@article {10770, title = {DEFB1 polymorphisms and HIV-1 mother-to-child transmission in Zambian population.}, journal = {J Matern Fetal Neonatal Med}, year = {2018}, month = {2018 Mar 20}, pages = {1-7}, abstract = {

INTRODUCTION: Human Beta Defensin-1 (hBD-1) is a component of the innate immune system, the first line of defence against pathogens, already reported as involved in the susceptibility to HIV-1 infection and HIV-1 mother-to-child transmission (MTCT) in different populations. We investigated the role of DEFB1 gene (encoding for hBD-1) functional polymorphisms in the susceptibility to HIV-1 MTCT in a population from Zambia.

METHODS: Four selected polymorphisms within DEFB1 gene, three at the 5{\textquoteright} untranslated region (UTR), namely -52G > A (rs1799946), -44C > G (rs1800972) and -20G > A (rs11362) and one in the 3{\textquoteright}UTR, c.*87A > G (rs1800972), were genotyped in 101 HIV-1 positive mothers (26 transmitters -27\% and 75 not transmitters -73\%) and 331 infants born to HIV-1 infected mothers (85 HIV-1 positive -26\% and 246 exposed but not infected -74\%).

RESULTS: DEFB1 c.*87-A allele was more frequent among HIV- children with respect to HIV+ (with intrauterine MTCT). Concerning DEFB1 haplotypes, GCGA haplotype resulted more represented in HIV- than HIV+ infants and DEFB1 ACGG haplotype presented increased frequency in HIV- children respect to HIV+ (with intra-partum MTCT) (p = .02, p = .002 and p = .006, respectively).

CONCLUSIONS: DEFB1 polymorphisms were significantly associated with decreased risk of HIV-1 infection acquisition in the studied Zambian population suggesting that they may play a role in HIV-1 MTCT.

}, issn = {1476-4954}, doi = {10.1080/14767058.2018.1449206}, author = {Zupin, Luisa and Polesello, Vania and Segat, Ludovica and Kamada, Anselmo Jiro and Kuhn, Louise and Crovella, Sergio} } @article {10471, title = {DEFB1 polymorphisms and salivary hBD-1 concentration in Oral Lichen Planus patients and healthy subjects.}, journal = {Arch Oral Biol}, volume = {73}, year = {2017}, month = {2017 Jan}, pages = {161-165}, abstract = {

OBJECTIVES: The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP.

DESIGN: We analysed three DEFB1 polymorphisms at 5{\textquoteright} UTR, -52G>A (rs1799946), -44C>G (rs1800972), -20G>A (rs11362) and two DEFB1 polymorphisms at 3{\textquoteright}UTR, c*5G>A (rs1047031), c*87A>G (rs1800971), with the aim of correlating these genetic variants and hBD-1 salivary level in a group of OLP patients and in healthy subjects. We also evaluated hBD-1 salivary concentrations, using ELISA, in OLP and healthy controls.

RESULTS: We compared hBD-1 concentrations in OLP and healthy subjects: hBD-1 concentration was significantly higher in OLP patients respect to control. When considering the correlation between DEFB1 polymorphisms genotypes and hBD-1 expression levels, significant results were obtained for SNPs -52G>A (p=0.03 both in OLP patients and healthy individuals) and -44C>G (p=0.02 in OLP patients).

CONCLUSIONS: hBD-1 production was different between OLP and healthy subjects (not age-matched with OLP). DEFB1 gene polymorphisms, -52G>A and -44C>G, correlated with hBD-1 salivary concentrations.

}, keywords = {5{\textquoteright} Untranslated Regions, Adult, Aged, Aged, 80 and over, beta-Defensins, Female, Genetic Predisposition to Disease, Genotype, Humans, Lichen Planus, Oral, Male, Middle Aged, Polymorphism, Single Nucleotide, Saliva, Sequence Analysis, DNA}, issn = {1879-1506}, doi = {10.1016/j.archoralbio.2016.10.008}, author = {Polesello, Vania and Zupin, Luisa and Di Lenarda, Roberto and Biasotto, Matteo and Pozzato, Gabriele and Ottaviani, Giulia and Gobbo, Margherita and Crovella, Sergio and Segat, Ludovica} } @article {8502, title = {CD209 promoter polymorphisms associate with HCV infection and pegylated-interferon plus ribavirin treatment response.}, journal = {Mol Immunol}, volume = {76}, year = {2016}, month = {2016 Aug}, pages = {49-54}, abstract = {

Hepatitis C is a severe liver disease caused by hepatitis C virus that could persist in the host causing progression towards chronic disease in about 80\% of the cases. Pegylated-interferon plus ribavirin was the gold standard therapy, however treatment{\textquoteright}s response was quite variable among individuals and different host/viral factors may play a role in disease outcome. The cluster of differentiation 209 (CD209 antigen) is a component of the innate immune system able to recognize HCV and consequently activating the immune response. We enrolled 203 Italian HCV infected patients and 220 healthy controls investigating if five promoter polymorphisms within CD209 gene (encoding for CD209 antigen) correlated with HCV infection susceptibility, spontaneous viral clearance and interferon treatment response. CD209 -939G>A and -871A>G polymorphisms associated with HCV infection susceptibility, while, CD209 -871A>G and -336A>G polymorphisms associated with response to treatment. In conclusion, CD209 polymorphisms could play a role in the susceptibility to HCV infection as well as interferon treatment response in our study population from North-East of Italy.

}, issn = {1872-9142}, doi = {10.1016/j.molimm.2016.06.009}, author = {Zupin, Luisa and Polesello, Vania and Alberi, Giulia and Moratelli, Giulia and Croc{\`e}, Saveria Lory and Masutti, Flora and Pozzato, Gabriele and Crovella, Sergio and Segat, Ludovica} } @article {8320, title = {DEFB1 gene polymorphisms and tuberculosis in a Northeastern Brazilian population.}, journal = {Braz J Microbiol}, volume = {47}, year = {2016}, month = {2016 Apr-Jun}, pages = {389-93}, abstract = {

β-Defensin-1, an antimicrobial peptide encoded by the DEFB1 gene, is known to play an important role in lung mucosal immunity. In our association study we analyzed three DEFB1 functional polymorphisms -52G>A (rs1799946), -44C>G (rs1800972) and -20G>A (rs11362) in 92 tuberculosis patients and 286 healthy controls, both from Northeast Brazil: no association was found between the studied DEFB1 polymorphisms and the disease. However we cannot exclude that this lack of association could be due to the low number of subjects analyzed, as suggested by the low statistical power achieved for the three analyzed SNPs (values between 0.16 and 0.50).

}, issn = {1678-4405}, doi = {10.1016/j.bjm.2015.09.001}, author = {Celerino da Silva, Ronaldo and da Cruz, Heidi Lacerda Alves and Brand{\~a}o, Lucas Andr{\'e} Cavalcanti and Guimar{\~a}es, Rafael Lima and Montenegro, Lilian Maria Lapa and Schindler, Haiana Charifker and Segat, Ludovica and Crovella, Sergio} } @article {8486, title = {DEFB1 polymorphisms and susceptibility to recurrent tonsillitis in Italian children.}, journal = {Int J Pediatr Otorhinolaryngol}, volume = {83}, year = {2016}, month = {2016 Apr}, pages = {12-5}, abstract = {

INTRODUCTION: The tonsils are secondary lymphoid organs fundamental for immune system response against pathogens within the oral cavity. Tonsillitis refers to inflammation of the pharyngeal tonsils that may include the adenoids and the lingual tonsils and that can be acute, recurrent, and chronic. Viral or bacterial infections, as well as immunologic factors are the main trigger to tonsillitis and disease{\textquoteright}s chronicity: the host immune responses, especially the innate one, could play an important role in susceptibility to the disease.

OBJECTIVES: The current study aims at investigating the role of functional polymorphisms in the 5{\textquoteright}UTR (c.-52G>A, c.-44G>C and c.-20G>A) of DEFB1 gene, encoding for the antimicrobial peptide human beta-defensin 1, in the predisposition to recurrent tonsillitis in children from North Eastern Italy.

RESULTS: No significant correlation was found between DEFB1 allele, genotype and haplotype frequencies and recurrent tonsillitis susceptibility with the exception of an increased risk to disease development in patients carrying DEFB1 rare haplotypes.

CONCLUSION: Our results may suggest that DEFB1 polymorphisms alone may not influence pathology susceptibility, however they could possibly concur, together with other factors involved in the genetic control of innate immune system, in the predisposition towards recurrent tonsillitis.

}, issn = {1872-8464}, doi = {10.1016/j.ijporl.2016.01.025}, author = {Zupin, Luisa and Polesello, Vania and Grasso, Domenico Leonardo and Crovella, Sergio and Segat, Ludovica} } @article {8287, title = {MBL2 genetic polymorphisms and HIV-1 mother-to-child transmission in Zambia.}, journal = {Immunol Res}, volume = {64}, year = {2016}, month = {2016 Jun}, pages = {775-84}, abstract = {

Since antiretroviral drugs have been introduced to prevent mother-to-child transmission, the risk of HIV-1 infection in infants has decreased considerably worldwide. Nevertheless, many factors are involved in viral transmission and host susceptibility to infection. The immune system and its components, including mannose binding protein C (encoding by MBL2 gene), are already known to play an important role in this scenario. In the present study, 313 children and 98 of their mothers from Zambia were genotyped for the MBL2 promoter HL (rs11003125) and XY (rs7096206) polymorphisms and exon 1 D (rs5030737, at codon 52) B (rs1800450, at codon 54) and C (rs1800451, at codon 57) polymorphisms in order to investigate the potential role of these genetic variants in HIV-1 mother-to-child transmission. No statistical significant association was observed comparing transmitter and non-transmitter mothers and also confronting HIV-positive and HIV-negative children. The findings of the current study obtained on mother and children from Zambia evidence lack of association between MBL2 functional polymorphisms and HIV-1 mother-to-child transmission.

}, issn = {1559-0755}, doi = {10.1007/s12026-015-8779-1}, author = {Zupin, Luisa and Polesello, Vania and Segat, Ludovica and Kuhn, Louise and Crovella, Sergio} } @article {8306, title = {Protective Role of BST2 Polymorphisms in Mother-to-Child Transmission of HIV-1 and Adult AIDS Progression.}, journal = {J Acquir Immune Defic Syndr}, volume = {72}, year = {2016}, month = {2016 Jul 1}, pages = {237-41}, abstract = {

Bone marrow stromal cell antigen-2 (BST-2)/Tetherin is a restriction factor that prevents Human immunodeficiency virus type 1 (HIV-1) release from infected cells and mediates pro-inflammatory cytokine production. This study investigated the risk conferred by single nucleotide polymorphisms (rs919266, rs9192677, and rs9576) at BST-2 coding gene (BST2) in HIV-1 mother-to-child transmission and in disease progression. Initially, 101 HIV-1+ pregnant women and 331 neonates exposed to HIV-1 from Zambia were enrolled. Additional BST2 single nucleotide polymorphism analyses were performed in 2 cohorts with acquired immunodeficiency syndrome (AIDS) progression: an adult Brazilian cohort (37 rapid, 30 chronic and 21 long-term non-progressors) and an Italian pediatric cohort (21 rapid and 67 slow progressors). The rs9576A allele was nominally associated with protection during breastfeeding (P = 0.019) and individuals carrying rs919266 GA showed slower progression to AIDS (P = 0.033). Despite the influence of rs919266 and rs9576 on BST2 expression being still undetermined, a preventive role by BST2 polymorphisms was found during HIV-1 infection.

}, issn = {1944-7884}, doi = {10.1097/QAI.0000000000000949}, author = {Kamada, Anselmo J and Bianco, Anna M and Zupin, Luisa and Girardelli, Martina and Matte, Maria C C and Medeiros, R{\'u}bia Mar{\'\i}lia de and Almeida, Sabrina Esteves de Matos and Rocha, Marineide M and Segat, Ludovica and Chies, Jos{\'e} A B and Kuhn, Louise and Crovella, Sergio} } @article {3626, title = {HLA-G and susceptibility to develop celiac disease.}, journal = {Hum Immunol}, volume = {76}, year = {2015}, month = {2015 Jan}, pages = {36-41}, abstract = {

The Human Leukocyte Antigen-G has immunomodulatory function and its expression has been associated with several diseases. In our study we analyzed HLA-G polymorphisms in order to evaluate their possible association with susceptibility to celiac disease development. A total of 420 celiac patients and 509 controls were genotyped for HLA-G polymorphisms. We sequenced 800bp upstream the ATG codon (5{\textquoteright} upstream regulatory region) and the whole 3{\textquoteright} untranslated region of the HLA-G gene, whereas the ΔC deletion at exon 3 was detected by RFLP-PCR. Five polymorphisms (namely -477 C>G, -369 C>A, 14bp del/ins, 3187 A>G, 3196 C>G) and one haplotype (TCGGTACGAAITCCCGAG) were significantly more frequent in celiac patients than controls and associated with increased disease susceptibility. The 14bp I/I, 3187 G/G, 3196 G/G genotypes and TCGGTACGAAITCCCGAG haplotype, were still significantly associated with increased disease susceptibility (and in addition also the 3003 C/C genotype) when the analysis was restricted to patients and controls presenting the DQ2.5 or DQ8 HLA-DQ celiac disease risk haplotypes. Our findings indicate an association between HLA-G gene polymorphisms and susceptibility to celiac disease development, suggesting that HLA-G molecule is possibly involved in the pathogenesis of the disease.

}, keywords = {Adolescent, Adult, Alleles, Case-Control Studies, Celiac Disease, Child, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, HLA-DQ Antigens, HLA-G Antigens, Humans, Male, Middle Aged, Polymorphism, Genetic, Retrospective Studies}, issn = {1879-1166}, doi = {10.1016/j.humimm.2014.12.006}, author = {Catamo, Eulalia and Zupin, Luisa and Segat, Ludovica and Celsi, Fulvio and Crovella, Sergio} } @article {7684, title = {Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration.}, journal = {Arch Oral Biol}, volume = {60}, year = {2015}, month = {2015 Jul}, pages = {1054-8}, abstract = {

OBJECTIVES: Human β-defensin 1 (hBD-1) is an antimicrobial peptide involved in epithelial defence of various tissues, also present in the saliva. Individual genetic variations within the DEFB1 gene, encoding for hBD-1, could influence gene expression and protein production.

DESIGN: Three DEFB1 polymorphisms at 5{\textquoteright} untranslated region (UTR), -52G > A (rs1799946), -44C > G (rs1800972) and -20G > A (rs11362), and two polymorphisms at DEFB1 3{\textquoteright} UTR, c*5G > A (rs1047031) and c*87A > G (rs1800971), were analysed by direct sequencing and correlated with hDB-1 salivary concentration (tested with enzyme-linked immunosorbent assay (ELISA)) in 40 healthy subjects.

RESULTS: Significant associations were found between individuals presenting different DEFB1 polymorphisms at positions -52 and -44 of the gene and hBD-1 salivary concentrations: -52 G/G carriers had higher levels of protein than G/A and A/A; -44C/G subjects showed a higher protein concentration than homozygous wild-type C/C. For the -20G > A, c*5G > A and c*87A > G polymorphisms, no statistically significant differences were found. Combined haplotype analysis confirmed the results obtained considering the single-nucleotide polymorphisms (SNPs) singularly.

CONCLUSION: Polymorphisms in the DEFB1 gene influence hBD-1 production and, therefore, could modify the innate immune system responses and, consequently, the oral health.

}, issn = {1879-1506}, doi = {10.1016/j.archoralbio.2015.03.009}, author = {Polesello, Vania and Zupin, Luisa and Di Lenarda, Roberto and Biasotto, Matteo and Ottaviani, Giulia and Gobbo, Margherita and Cecco, Luca and Alberi, Giulia and Pozzato, Gabriele and Crovella, Sergio and Segat, Ludovica} } @article {3616, title = {Interleukin-18 gene promoter polymorphisms and celiac disease in Italian patients.}, journal = {Mol Biol Rep}, volume = {42}, year = {2015}, month = {2015 Feb}, pages = {525-33}, abstract = {

Celiac disease (CD) is the most common food-sensitive enteropathy in genetically susceptible individuals. The major genetic risk factors known are specific human leukocyte antigen (HLA)-DQ haplotypes, but other genetic factors are supposed to be involved. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that has an important role in the immune defense and it has the potential to influence inflammatory disorders. IL-18 is able to promote Th1 cell development and it is expressed in the mucosa of the small intestine in celiac patients. Given the IL-18 biological role, and since a few studies have previously suggested its involvement in CD, in order to investigate the role of IL18 gene in the susceptibility to CD we have performed a case-control study, analyzing two IL18 gene promoter polymorphisms, previously reported to impair the transcriptional activity of the gene, (-137G > C and -607C > A, rs187238 and rs1946518 respectively). A total of 556 CD Italian patients and 582 controls, further stratified for HLA class II (DQ) CD risk haplotypes were enrolled. The -607A > C A allele and A/A genotype, as well as the combination of this allele with the -137G allele in the AG haplotype, were associated with an increased risk towards CD development, in particular in HLA-DQ2.2 patients. Although the association was very moderate, our results indicate the possible involvement of IL18 gene in the susceptibility to CD, and for this reason we do think it should deserve further investigation.

}, issn = {1573-4978}, doi = {10.1007/s11033-014-3796-z}, author = {Zupin, Luisa and Catamo, Eulalia and Polesello, Vania and Crovella, Sergio and Segat, Ludovica} } @article {7683, title = {Lactotransferrin gene functional polymorphisms do not influence susceptibility to human immunodeficiency virus-1 mother-to-child transmission in different ethnic groups.}, journal = {Mem Inst Oswaldo Cruz}, volume = {110}, year = {2015}, month = {2015 Apr}, pages = {222-9}, abstract = {

Lactotransferrin, also known as lactoferrin, is an iron binding glycoprotein that displays antiviral activity against many different infectious agents, including human immunodeficiency virus (HIV)-1. Lactotransferrin is present in the breast milk and in the female genitourinary mucosa and it has been hypothesised as a possible candidate to prevent mother-to-child HIV-1 transmission. To verify if two functional polymorphisms, Thr29Ala and Arg47Lys, in the lactotransferrin encoding gene (LTF) could affect HIV-1 infection and vertical transmission, a preliminary association study was performed in 238 HIV-1 positive and 99 HIV-1 negative children from Brazil, Italy, Africa and India. No statistically significant association for the Thr29Ala and Arg47Lys LTF polymorphisms and HIV-1 susceptibility in the studied populations was found. Additionally LTF polymorphisms frequencies were compared between the four different ethnic groups.

}, keywords = {Acquired Immunodeficiency Syndrome, Adolescent, Brazil, Child, Cohort Studies, Ethnic Groups, Female, Gene Frequency, Genetic Predisposition to Disease, Genotyping Techniques, HIV-1, Humans, India, Infant, Newborn, Infectious Disease Transmission, Vertical, Italy, Lactoferrin, Male, Polymorphism, Single Nucleotide, Real-Time Polymerase Chain Reaction, Retrospective Studies, Zimbabwe}, issn = {1678-8060}, doi = {10.1590/0074-02760140447}, author = {Zupin, Luisa and Polesello, Vania and Coelho, Ant{\^o}nio Victor Campos and Boniotto, Michele and Arraes, Luiz Claudio and Segat, Ludovica and Crovella, Sergio} } @article {7758, title = {MBL2 polymorphisms in women with atypical squamous cells of undetermined significance.}, journal = {J Med Virol}, volume = {87}, year = {2015}, month = {2015 May}, pages = {851-9}, abstract = {

Infection with high risk Human papillomavirus (HPV) is the main known cause of cervical cancer. HPV induces different grades of lesions: among them, Atypical squamous cells of undetermined significance are abnormal lesions that could evolve in pre-cancer lesions or spontaneously regress. The mannose binding lectin (MBL) is an innate immunity serum protein also found in cervico-vaginal mucosa, whose expression is known to be affected by polymorphisms in exon 1 and promoter of the MBL2 gene. In the present study the possible association between MBL2 functional polymorphisms and susceptibility to develop atypical squamous cells of undetermined significance was investigated in a group of women from North-East of Italy, stratified for HPV infection status. The MBL2 D and O alleles and the deficient producer combined genotypes, responsible for low MBL production, were more represented among atypical squamous cells of undetermined significance positive women than healthy controls and the results were confirmed when only HPV negative samples were considered. These results suggest a possible involvement of MBL2 functional polymorphisms in atypical squamous cells of undetermined significance susceptibility.

}, keywords = {Adolescent, Adult, Atypical Squamous Cells of the Cervix, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Italy, Mannose-Binding Lectin, Polymorphism, Single Nucleotide, Young Adult}, issn = {1096-9071}, doi = {10.1002/jmv.24080}, author = {Zupin, Luisa and Polesello, Vania and Casalicchio, Giorgia and Freato, Nadia and Maestri, Iva and Comar, Manola and Crovella, Sergio and Segat, Ludovica} } @article {3530, title = {Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population.}, journal = {Mol Biol Rep}, volume = {41}, year = {2014}, month = {2014 Aug}, pages = {5449-57}, abstract = {

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for association with TB in a Northeastern Brazilian population (295 subjects, 131~TB patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated with susceptibility to TB, and in particular with pulmonary and extra-pulmonary forms respectively. The -871A>G and -336A>G SNPs were associated, the first with protection to both pulmonary and extra-pulmonary TB, the latter only with the pulmonary form. An association between GGAG haplotype and protection to TB infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was associated with TB infection. This study provides evidence of an association between CD209 and CD209L polymorphisms and TB development in a Brazilian population, suggesting that variations in these genes may influence the protection and susceptibility to infection caused by M. tuberculosis.

}, keywords = {Adult, Alleles, Brazil, Case-Control Studies, Cell Adhesion Molecules, Dendritic Cells, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Lectins, C-Type, Male, Mycobacterium tuberculosis, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Receptors, Cell Surface, Tuberculosis, Young Adult}, issn = {1573-4978}, doi = {10.1007/s11033-014-3416-y}, author = {da Silva, Ronaldo Celerino and Segat, Ludovica and da Cruz, Heidi Lacerda Alves and Schindler, Haiana Charifker and Montenegro, Lilian Maria Lapa and Crovella, Sergio and Guimar{\~a}es, Rafael Lima} } @article {3490, title = {Beta defensin-1 gene polymorphisms and susceptibility to atypical squamous cells of undetermined significance lesions in Italian gynecological patients.}, journal = {J Med Virol}, volume = {86}, year = {2014}, month = {2014 Dec}, pages = {1999-2004}, abstract = {

The role of the human beta-defensin 1 (hBD-1) in the susceptibility to the onset of the Atypical Squamous Cells of Undetermined Significance (ASCUS) lesion, in the presence or not of HPV infection, is still unknown. In the current study, the three functional single nucleotide polymorphisms (SNPs) -52G > A, -44C > G, and -20G > A at the 5{\textquoteright} un-translated region (UTR) of DEFB1 gene, encoding hBD-1, were analyzed in ASCUS lesion gynecological patients and healthy women from the north-east of Italy (Trieste). Cervical samples from 249 European-Caucasian women were collected, screened for HPV and cytologically evaluated; DEFB1 genotyping has been performed by direct sequencing. No significant differences were found for -52G > A, -44C > G, and -20G > A SNPs allele and genotype frequencies between women with and without ASCUS lesions. DEFB1 minor haplotypes were significantly more frequent in ASCUS lesion positive than negative women, associating with an increased risk of this type of lesion. When women were stratified according to HPV infection status, significant differences in the distribution of -52G > A SNP genotype frequencies were found: the presence of the A allele in the homozygous genotype A/A associated with a lower risk of developing ASCUS lesions in HPV negative women. DEFB1 minor haplotypes were also associated with an increased risk of developing ASCUS lesions, being significantly more frequent in HPV negative women with lesions, than without lesions. Although these results highlight the possible involvement of DEFB1, further studies are needed to support the role of DEFB1 in the modulation of the susceptibility to ASCUS lesions.

}, keywords = {5{\textquoteright} Untranslated Regions, Adolescent, Adult, Atypical Squamous Cells of the Cervix, beta-Defensins, Female, Genotype, Humans, Italy, Papillomavirus Infections, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Uterine Cervical Neoplasms, Young Adult}, issn = {1096-9071}, doi = {10.1002/jmv.23878}, author = {Casalicchio, Giorgia and Freato, Nadia and Maestri, Iva and Comar, Manola and Crovella, Sergio and Segat, Ludovica} } @article {3623, title = {DEFB1 polymorphisms are involved in susceptibility to human papillomavirus infection in Brazilian gynaecological patients.}, journal = {Mem Inst Oswaldo Cruz}, volume = {109}, year = {2014}, month = {2014 Nov}, pages = {918-22}, abstract = {

The human beta defensin 1 (hBD-1) antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV). In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5{\textquoteright}UTR and c.*5G>A and c.*87A>G in the 3{\textquoteright}UTR) in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs) and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.

}, keywords = {Adolescent, Adult, Aged, beta-Defensins, Brazil, Case-Control Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Middle Aged, Papillomavirus Infections, Polymorphism, Single Nucleotide, Reproductive Tract Infections, Young Adult}, issn = {1678-8060}, author = {Segat, Ludovica and Zupin, Luisa and Moura, Ronald Rodrigues and Coelho, Ant{\^o}nio Victor Campos and Chagas, B{\'a}rbara Simas and de Freitas, Antonio Carlos and Crovella, Sergio} } @article {3523, title = {Interleukin-10 gene promoter polymorphisms in celiac patients from north-eastern Italy.}, journal = {Hum Immunol}, volume = {75}, year = {2014}, month = {2014 Jul}, pages = {656-61}, abstract = {

Celiac disease is a complex chronic intestinal disorder driven by an immune response against the gliadin fraction of gluten: many factors are involved in the pathogenesis of the disease, and among these Interleukin-10 could play an important role. In the present study, the -1082A>G, -819T>C and -592A>C IL10 functional polymorphisms were analyzed in 565 celiac patients and 576 healthy controls from north-eastern Italy, stratified for HLA class II celiac disease risk haplotypes. No significant differences were observed for the three IL10 polymorphisms distribution between celiac patients and controls with the exception of a slightly increased risk for the -1082A allele in HLA-DQ8 male individuals. Although our findings suggest that the IL10 genetic variants analyzed do not have a major role in the susceptibility to the development of celiac disease in north-eastern Italian patients, we think that the possible involvement of IL10 gene in CD should deserve further investigation and that large-scale studies are recommended to confirm our findings.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Case-Control Studies, Celiac Disease, Child, Child, Preschool, European Continental Ancestry Group, Female, Gene Frequency, HLA-DQ Antigens, Humans, Interleukin-10, Italy, Male, Middle Aged, Models, Genetic, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Risk Factors, Sex Factors}, issn = {1879-1166}, doi = {10.1016/j.humimm.2014.04.011}, author = {Zupin, Luisa and Polesello, Vania and Catamo, Eulalia and Crovella, Sergio and Segat, Ludovica} } @article {3603, title = {Non-classical MHC-I human leukocyte antigen (HLA-G) in hepatotropic viral infections and in hepatocellular carcinoma.}, journal = {Hum Immunol}, volume = {75}, year = {2014}, month = {2014 Dec}, pages = {1225-31}, abstract = {

The human leukocyte antigen (HLA)-G is a "nonclassical" major histocompatibility complex (MHC) class Ib gene, located at chromosome 6, in the 6p21.3 region. The HLA-G presents immunomodulatory functions essential in pregnancy for the tolerance of the semi-allogenic fetus, but an abnormal expression of HLA-G has been observed in numerous pathological conditions, such as tumors, autoimmune diseases and viral infections. In recent years, numerous studies have assessed the clinical relevance of HLA-G expression in different types of cancer: in general, a higher HLA-G expression correlates with a lower survival rate or a shorter disease-free survival. Altered expression of HLA-G has been found in both HCV and HBV infection, and some genetic polymorphisms have been associated with altered susceptibility/disease development for these infections, however, whether the biologic role of HLA-G in HCV and HBV infection is beneficial or hazardous, it is not completely clear. In the context of hepatocellular carcinoma, HLA-G has shown a potential diagnostic role, moreover a prognostic value in HCC patients has been also attributed to HLA-G molecules. We revise here the role of HLA-G in hepatotropic HBV/HCV infections and in hepatocellular carcinoma (HCC).

}, keywords = {Carcinoma, Hepatocellular, Female, Genetic Predisposition to Disease, Hepatitis B, Hepatitis C, HLA-G Antigens, Humans, Immune Tolerance, Liver Neoplasms, Polymorphism, Genetic, Pregnancy}, issn = {1879-1166}, doi = {10.1016/j.humimm.2014.09.019}, author = {Catamo, Eulalia and Zupin, Luisa and Crovella, Sergio and Celsi, Fulvio and Segat, Ludovica} } @article {8098, title = {The p53 transcriptional pathway is preserved in ATMmutated and NOTCH1mutated chronic lymphocytic leukemias.}, journal = {Oncotarget}, volume = {5}, year = {2014}, month = {2014 Dec 30}, pages = {12635-45}, abstract = {

By using next generation sequencing, we have analyzed 108 B chronic lymphocytic leukemia (B-CLL) patients. Among genes involved in the TP53 pathway, we found frequent mutations in ATM (n=18), TP53 (n=10) and NOTCH1 (n=10) genes, rare mutations of NOTCH2 (n=2) and CDKN1A/p21 (n=1) and no mutations in BAX, MDM2, TNFRSF10A and TNFRSF10B genes. The in vitro treatment of primary B-CLL cells with the activator of p53 Nutlin-3 induced the transcription of p53 target genes, without significant differences between the B-CLL without mutations and those harboring either ATM or NOTCH1mutations. On the other hand, the subgroup of TP53mutated B-CLL exhibited a significantly lower induction of the p53 target genes in response to Nutlin-3 as compared to the other B-CLL samples. However, among the TP53mutated B-CLL, those showing mutations in the high hot spot region of the DNA binding domain [273-280 aa] maintained a significantly higher p53-dependent transcriptional activity as compared to the other TP53mutated B-CLL samples. Since the ability to elicit a p53-dependent transcriptional activity in vitro has a positive prognostic significance, our data suggest that ATMmutated, NOTCH1mutated and surprisingly, also a subset of TP53mutated B-CLL patients might benefit from therapeutic combinations including small molecule activator of the p53 pathway.

}, keywords = {Aged, Aged, 80 and over, Ataxia Telangiectasia Mutated Proteins, Base Sequence, Female, Genes, p53, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Models, Molecular, Molecular Sequence Data, Mutation, Receptor, Notch1, Signal Transduction, Tumor Suppressor Protein p53}, issn = {1949-2553}, doi = {10.18632/oncotarget.2211}, author = {Athanasakis, Emmanouil and Melloni, Elisabetta and Rigolin, Gian Matteo and Agnoletto, Chiara and Voltan, Rebecca and Vozzi, Diego and Piscianz, Elisa and Segat, Ludovica and dal Monego, Simeone and Cuneo, Antonio and Secchiero, Paola and Zauli, Giorgio} } @article {1898, title = {DEFB1 gene 5{\textquoteright} untranslated region (UTR) polymorphisms in inflammatory bowel diseases.}, journal = {Clinics (Sao Paulo)}, volume = {67}, year = {2012}, month = {2012}, pages = {395-8}, keywords = {5{\textquoteright} Untranslated Regions, Adult, Antimicrobial Cationic Peptides, beta-Defensins, Case-Control Studies, Colitis, Ulcerative, Crohn Disease, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Inflammatory Bowel Diseases, Male, Polymorphism, Genetic, Polymorphism, Single Nucleotide}, issn = {1980-5322}, author = {Zanin, Valentina and Segat, Ludovica and Bianco, Anna Monica and Padovan, Lara and Tavares, Nathalia de Alencar Cunha and Crovella, Sergio} } @article {1963, title = {Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population.}, journal = {Hum Immunol}, volume = {73}, year = {2012}, month = {2012 Nov}, pages = {1159-65}, abstract = {

DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and placental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmission, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 positive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (-139G>A, -201G>T and -336A>G) were significantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indicating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission.

}, keywords = {Alleles, Brazil, Cell Adhesion Molecules, Child, Child, Preschool, Exons, Female, Gene Frequency, Genotype, HIV Infections, HIV-1, Humans, Infectious Disease Transmission, Vertical, Lectins, C-Type, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Receptors, Cell Surface, Tandem Repeat Sequences}, issn = {1879-1166}, doi = {10.1016/j.humimm.2012.07.338}, author = {da Silva, Ronaldo Celerino and Segat, Ludovica and Zanin, Valentina and Arraes, Luiz Claudio and Crovella, Sergio} } @article {1877, title = {A real-time polymerase chain reaction-based protocol for low/medium-throughput Y-chromosome microdeletions analysis.}, journal = {Genet Test Mol Biomarkers}, volume = {16}, year = {2012}, month = {2012 Dec}, pages = {1349-55}, abstract = {

PURPOSE: We describe a real-time polymerase chain reaction (PCR) protocol based on the fluorescent molecule SYBR Green chemistry, for a low- to medium-throughput analysis of Y-chromosome microdeletions, optimized according to the European guidelines and aimed at making the protocol faster, avoiding post-PCR processing, and simplifying the results interpretation.

METHODS: We screened 156 men from the Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Institute for Maternal and Child Health IRCCS Burlo Garofolo (Trieste, Italy), 150 not presenting Y-chromosome microdeletion, and 6 with microdeletions in different azoospermic factor (AZF) regions. For each sample, the Zinc finger Y-chromosomal protein (ZFY), sex-determining region Y (SRY), sY84, sY86, sY127, sY134, sY254, and sY255 loci were analyzed by performing one reaction for each locus.

RESULTS: AZF microdeletions were successfully detected in six individuals, confirming the results obtained with commercial kits.

CONCLUSION: Our real-time PCR protocol proved to be a rapid, safe, and relatively cheap method that was suitable for a low- to medium-throughput diagnosis of Y-chromosome microdeletion, which allows an analysis of approximately 10 samples (with the addition of positive and negative controls) in a 96-well plate format, or approximately 46 samples in a 384-well plate for all markers simultaneously, in less than 2 h without the need of post-PCR manipulation.

}, keywords = {Azoospermia, Chromosome Deletion, Chromosomes, Human, Y, Female, Humans, Kruppel-Like Transcription Factors, Male, Real-Time Polymerase Chain Reaction, Sex Chromosome Aberrations, Sex Chromosome Disorders of Sex Development}, issn = {1945-0257}, doi = {10.1089/gtmb.2012.0220}, author = {Segat, Ludovica and Padovan, Lara and Doc, Darja and Petix, Vincenzo and Morgutti, Marcello and Crovella, Sergio and Ricci, Giuseppe} } @article {1821, title = {Frequency of HLA B*5701 allele carriers in abacavir treated-HIV infected patients and controls from northeastern Brazil.}, journal = {Clinics (Sao Paulo)}, volume = {66}, year = {2011}, month = {2011}, pages = {1485-8}, keywords = {Adolescent, Adult, Anti-HIV Agents, Brazil, Case-Control Studies, Dideoxynucleosides, Drug Hypersensitivity, Female, Gene Frequency, Genotype, HIV Infections, HLA-B Antigens, Humans, Male, Middle Aged, Real-Time Polymerase Chain Reaction, Young Adult}, issn = {1980-5322}, author = {Crovella, Sergio and Biller, Lara and Santos, Sergio and Salustiano, Ana and Brand{\~a}o, Lucas and Guimar{\~a}es, Rafael and Segat, Ludovica and Lima Filho, Jose Luiz de and Arraes, Luiz Claudio} } @article {1661, title = {HLA-G 14 bp deletion/insertion polymorphism in celiac disease.}, journal = {Am J Gastroenterol}, volume = {106}, year = {2011}, month = {2011 Jan}, pages = {139-44}, abstract = {

OBJECTIVES: Nonclassical major histocompatibility class I HLA-G antigen is a tolerogenic molecule that inhibits lytic activity of natural killer (NK) cells and cytotoxic T lymphocytes. Because of its immunomodulatory and tolerogenic properties, HLA-G molecules may have a role in celiac disease (CD). We analyzed the HLA-G 14 bp deletion/insertion polymorphism, known to have a functional effect on mRNA stability, in a group of 522 CD patients, stratified for the presence of HLA-DQ2 genotype, and 400 healthy individuals to evaluate the possible effect of the polymorphism on the risk to develop the disease.

METHODS: HLA-G 14 bp deletion/insertion polymorphism (rs1704) was detected by polymerase chain reaction and double-checked by direct sequencing.

RESULTS: The 14 bp inserted (I) allele and the homozygous I/I genotype were significantly more frequent in CD patients than in healthy controls. The presence of I allele was associated with an increased risk of CD (OR 1.35) and the effect of I allele was consistent with a recessive genetic model (P<0.001).

CONCLUSIONS: Our results also indicate that the effect of the HLA-G D/I polymorphism is restricted for HLA-DQ2, and not simply due to the presence of linkage disequilibrium with the major known risk factor; moreover we found that the presence of the I allele confers an increased risk of CD in addition to the risk conferred by HLA-DQ2 alone and that subjects that carry both DQ2 and HLA-G I alleles have an increased risk of CD than subjects that carry DQ2 but not the I allele.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Case-Control Studies, Celiac Disease, Child, Child, Preschool, Confidence Intervals, Female, Genetic Predisposition to Disease, Genotype, Histocompatibility Antigens Class I, HLA Antigens, HLA-DQ Antigens, HLA-G Antigens, Humans, Male, Middle Aged, Mutagenesis, Insertional, Odds Ratio, Polymerase Chain Reaction, Polymorphism, Genetic, Reference Values, RNA Stability, Sequence Deletion, Young Adult}, issn = {1572-0241}, doi = {10.1038/ajg.2010.340}, author = {Fabris, Annalisa and Segat, Ludovica and Catamo, Eulalia and Morgutti, Marcello and Vendramin, Anna and Crovella, Sergio} } @article {1746, title = {Mannose binding lectin gene (MBL2) functional polymorphisms are associated with systemic lupus erythematosus in southern Brazilians.}, journal = {Hum Immunol}, volume = {72}, year = {2011}, month = {2011 Jun}, pages = {516-21}, abstract = {

Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations.

}, keywords = {Adolescent, Adult, Aged, Brazil, DNA Mutational Analysis, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Lupus Erythematosus, Systemic, Male, Mannose-Binding Lectin, Middle Aged, Polymorphism, Genetic, Population Groups, Promoter Regions, Genetic}, issn = {1879-1166}, doi = {10.1016/j.humimm.2011.03.007}, author = {Sandrin-Garcia, Paula and Brand{\~a}o, Lucas Andr{\'e} Cavalcanti and Coelho, Ant{\^o}nio Victor Campos and Guimar{\~a}es, Rafael Lima and Pancoto, Jo{\~a}o Alexandre Tr{\'e}s and Segat, Ludovica and Donadi, Eduardo Ant{\^o}nio and de Lima-Filho, Jos{\'e} Luiz and Crovella, Sergio} } @article {1811, title = {MBL1 gene in nonhuman primates.}, journal = {Hum Immunol}, volume = {72}, year = {2011}, month = {2011 Nov}, pages = {1084-90}, abstract = {

With the aim of investigating the evolution of MBL1P1 (MBL1) gene, we analyzed the MBL1 coding region sequences in several specimens of two species of great apes, two species of Hylobatidae, four species of Cercopithecidae, and one Platyrrhine species, and in human beings. An indication for a progressive silencing of the molecule has been found. We found a \~{}300 bp insertion in the first intron of MBL1 in the Cercopithecidae that could explain the different splicing between primates species and possibly why Macaca mulatta is able to produce a complete protein, whereas in human beings the protein product is truncated. Based on our genetic findings, we could speculate that all the Cercopithecidae (presenting the 300-bp insertion) may express MBL1 mature protein like the M mulatta, whereas the lesser and great apes, which lack this insertion as do human beings, may have only the truncated pseudogene.

}, keywords = {Animals, Base Sequence, Evolution, Molecular, Gene Silencing, Genome, Humans, Mannose-Binding Lectin, Molecular Sequence Data, Multigene Family, Phylogeny, Polymorphism, Genetic, Primates, Pseudogenes, Sequence Alignment, Sequence Analysis, DNA, Sequence Deletion, Species Specificity}, issn = {1879-1166}, doi = {10.1016/j.humimm.2011.08.009}, author = {Segat, Ludovica and Crovella, Sergio} } @article {1752, title = {A polymorphism in PRF1 gene is associated with HIV-1 vertical transmission in Brazilian children.}, journal = {AIDS}, volume = {25}, year = {2011}, month = {2011 Feb 20}, pages = {535-7}, abstract = {

We investigated the possible association between PRF1 gene polymorphisms and HIV-1 vertical transmission in Brazilian children by analyzing PRF1 gene coding and untranslated regions in 173 perinatally infected children (HIV+), 51 exposed uninfected (HIV-), and 171 HIV-unexposed uninfected children. Seven single nucleotide polymorphisms were identified in our samples. The rs885822 C allele and CC genotype were significantly more frequent in HIV-negative than in HIV-positive patients and associated with a protective effect toward HIV vertical transmission.

}, keywords = {Brazil, Female, HIV Infections, HIV-1, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Male, Polymorphism, Genetic, Pore Forming Cytotoxic Proteins, Pregnancy}, issn = {1473-5571}, doi = {10.1097/QAD.0b013e3283428b7c}, author = {Padovan, Lara and Segat, Ludovica and Crovella, Sergio} } @article {1644, title = {A polymorphism in the 5{\textquoteright} UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients.}, journal = {Clin Chem Lab Med}, volume = {49}, year = {2011}, month = {2011 Jan}, pages = {49-54}, abstract = {

BACKGROUND: The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5{\textquoteright} untranslated region (5{\textquoteright} UTR) of the β defensin 1 (DEFB1) gene and the CF pulmonary phenotype.

METHODS: Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan({\textregistered}) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42).

RESULTS: For the c.-20G>A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G>A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients.

CONCLUSIONS: Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.

}, keywords = {5{\textquoteright} Untranslated Regions, Adult, beta-Defensins, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Female, Genotype, Homozygote, Humans, Italy, Male, Mutation, Phenotype, Polymorphism, Genetic, Young Adult}, issn = {1437-4331}, doi = {10.1515/CCLM.2011.023}, author = {Crovella, Sergio and Segat, Ludovica and Amato, Annalisa and Athanasakis, Emmanouil and Bezzerri, Valentino and Braggion, Cesare and Casciaro, Rosaria and Castaldo, Giuseppe and Colombo, Carla and Covone, Angela Elvira and De Rose, Virginia and Gagliardini, Rolando and Lanzara, Carmen and Minicucci, Laura and Morgutti, Marcello and Nicolis, Elena and Pardo, Francesca and Quattrucci, Serena and Raia, Valeria and Ravazzolo, Roberto and Seia, Manuela and Stanzial, Valentino and Termini, Lisa and Zazzeron, Laura and Cabrini, Giulio and Gasparini, Paolo} } @article {1748, title = {Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission.}, journal = {Hum Immunol}, volume = {72}, year = {2011}, month = {2011 Apr}, pages = {305-11}, abstract = {

The innate immune system acts in the first line of host defense against pathogens. One of the mechanisms used involves the early recognition and uptake of microbes by host professional phagocytes, through pattern recognition receptors (PRRs). These PRRs bind to conserved microbial ligands expressed by pathogens and initiate both innate and adaptative immune responses. Some PRRs located on the surface of dendritic cells (DCs) and other cells seem to play an important role in human immunodeficiency virus type 1 (HIV-1) transmission. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin, CD209 (DC-SIGN) and its homolog, DC-SIGN-related (DC-SIGNR or L-SIGN) receptors are PPRs able to bind the HIV-1 gp120 envelope protein and, because alterations in their expression patterns also occur, they might play a role in both horizontal and vertical transmission as well as in disseminating the virus within the host. This review aims to explore the involvement of the DC-SIGN and L-SIGN receptors in HIV-1 transmission from mother to child.

}, keywords = {Cell Adhesion Molecules, HIV Infections, HIV-1, Humans, Immunity, Innate, Infectious Disease Transmission, Vertical, Lectins, C-Type, Polymorphism, Genetic, Receptors, Cell Surface}, issn = {1879-1166}, doi = {10.1016/j.humimm.2011.01.012}, author = {da Silva, Ronaldo Celerino and Segat, Ludovica and Crovella, Sergio} } @article {1721, title = {The significance of mannose-binding lectin gene polymorphisms on the risk of BK virus coinfection in women with human papillomavirus-positive cervical lesions.}, journal = {Hum Immunol}, volume = {72}, year = {2011}, month = {2011 Aug}, pages = {663-6}, abstract = {

The simultaneous detection of oncogenic human papillomavirus (HPV) and BK virus (BKV) has been recently reported in cervical cancers, suggesting that these viruses may act together in the process of cell transformation; host genetic polymorphisms may also influence virus persistence/reactivation. To disclose a possible role of the gene encoding for the mannose-binding lectin, MBL2, in susceptibility to BKV infection, we analyzed functional polymorphisms in the first exon of MBL2 in women stratified for the presence/absence of BKV and affected by different grades of HPV-induced cervical precancerous lesions. All BKV-positive samples were also HPV positive (HPV 16), and all presented with high-grade squamous intraepithelial lesions. The MBL2 A allele was significantly more frequent in BKV-negative patients than in BKV-positive patients. These data indicate a possible role for the A allele in conferring protection to BKV infection in high-risk HPV-positive women (odds ratio 0.40, 95\% confidence interval 0.20-0.85, p = 0.01).

}, keywords = {Adult, Aged, Alleles, BK Virus, Cervical Intraepithelial Neoplasia, Cervix Uteri, DNA Fingerprinting, DNA, Viral, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Human papillomavirus 16, Humans, Italy, Mannose-Binding Lectin, Odds Ratio, Papillomavirus Infections, Polymorphism, Genetic, Polyomavirus Infections, Risk, Viral Load}, issn = {1879-1166}, doi = {10.1016/j.humimm.2011.04.002}, author = {Comar, Manola and Segat, Ludovica and Crovella, Sergio and Bovenzi, Massimo and Cortini, Enzo and Tognon, Mauro} } @article {1611, title = {Tag-single nucleotide polymorphism-based human leukocyte antigen genotyping in celiac disease patients from northeastern Italy.}, journal = {Hum Immunol}, volume = {72}, year = {2011}, month = {2011 Jun}, pages = {499-502}, abstract = {

We genotyped celiac disease (CD)-associated haplotypes DQ2.5, DQ8, DQ2.2, and DQ7 in 1005 CD patients from North Eastern Italy using a Tag-single nucleotide polymorphism (SNPs) approach and real time PCR platform, checking the accuracy and reliability of the method and comparing it to traditional PCR-SSP. Only 14 of 2010 chromosomes analyzed (0.7\%) showed discrepancies between the Tag-SNPs real-time polymerase chain reaction (PCR) method and the PCR-single-strand polymorphism (SSP) technique, indicating a high sensitivity and specificity (ranging from 0.987 to 1 and from 0.998 to 0.999, respectively) for tagging with respect to corresponding human leukocyte antigen (HLA) alleles identified by PCR-SSP. Moreover, the overall cost of the Tag-SNPs HLA typing method was low (3 to 4 {\texteuro}/sample instead of 35 to 70 {\texteuro}/sample with commercial kits), making it suitable for mass screenings. Hence, we believe that the Tag-SNPs HLA typing could be used to complement or replace classic HLA typing in at high-risk groups, for research purposes and eventually in population screening programs.

}, keywords = {Adolescent, Adult, Aged, Celiac Disease, Child, Child, Preschool, Female, Humans, Infant, Italy, Male, Mass Screening, Middle Aged, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity}, issn = {1879-1166}, doi = {10.1016/j.humimm.2011.03.008}, author = {Vatta, Serena and Fabris, Annalisa and Segat, Ludovica and Not, Tarcisio and Crovella, Sergio} } @article {1689, title = {A 3{\textquoteright}UTR SNP in NLRP3 gene is associated with susceptibility to HIV-1 infection.}, journal = {J Acquir Immune Defic Syndr}, volume = {54}, year = {2010}, month = {2010 Jul}, pages = {236-40}, abstract = {

OBJECTIVES: Innate immunity genes polymorphisms are known to be involved in the multifactorial susceptibility to HIV-1 infection. Recently it has been hypothesized that inflammasomes could play an important role in the host response to viruses. The aim of our study is to verify if single-nucleotide polymorphisms (SNPs) in genes encoding for NALPs-innate immune receptors that form molecular complexes leading to the production of IL-1beta and the activation of immune response-could influence the individual susceptibility to HIV-1.

DESIGN: We performed an association study analyzing 2 NLRP1 and NLRP3 SNPs in HIV-1 vertically infected Brazilian children (n = 135), HIV-1-infected Brazilain adults (n = 192) and HIV-1-positive Italian seropositive subjects (n = 192).

RESULTS: The 3{\textquoteright}UTR NLRP3 rs10754558 SNP was associated with HIV-1 infection in all the studied groups. The frequency of rs10754558 G allele was differently distributed within seropositive subjects (HIV+) and controls, and in particular the GG genotype was less frequent in HIV+.

CONCLUSIONS: susceptibility to HIV-1 infection is associated with a 3{\textquoteright}UTR NLRP3 polymorphism. This is the first report linking SNPs in the NALPs with HIV-1 infection, and further epidemiologic and functional studies are needed to deeper investigate the role of inflammasome in the susceptibility to HIV-1 infection.

}, keywords = {Adult, Brazil, Carrier Proteins, Case-Control Studies, Child, Child, Preschool, Female, Genetic Predisposition to Disease, Genotype, HIV Infections, HIV-1, Humans, Infant, Infectious Disease Transmission, Vertical, Male, Middle Aged, Polymorphism, Single Nucleotide, Pregnancy, Young Adult}, issn = {1944-7884}, doi = {10.1097/QAI.0b013e3181dd17d4}, author = {Pontillo, Alessandra and Brand{\~a}o, Lucas A and Guimar{\~a}es, Rafael L and Segat, Ludovica and Athanasakis, Emmanouil and Crovella, Sergio} } @article {1701, title = {Beta defensin-1 gene (DEFB1) polymorphisms are not associated with atopic dermatitis in children and adolescents from northeast Brazil (Recife, Pernambuco).}, journal = {Int J Dermatol}, volume = {49}, year = {2010}, month = {2010 Jun}, pages = {653-7}, abstract = {

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease resulting from the interplay between environmental, immunological and genetic factors. In our study, we investigated the role of three single nucleotide polymorphisms (SNPs) at 5{\textquoteright}-UTR of DEFB1 gene, encoding for the human beta defensin-1, on the susceptibility to develop AD in a group of Brazilian children and adolescents.

METHODS: Three SNPs, -20 G/A (rs11362), -44 C/G (rs1800972), and -52 G/A (rs1799946) at 5{\textquoteright}-UTR of DEFB1 gene were genotyped in two groups of children and adolescents, one affected by AD (96 subjects), the other healthy (191 individuals), from northeast Brazil.

RESULTS: -44 C/G frequencies were comparable between the two groups. The -20 GG genotype was more frequent in AD subjects than in healthy controls; the -52 GG, conversely, was more frequent in healthy controls than in AD. However, both these differences did not reach statistical significance. Also, association between SNPs and AD severity has been shown. The analysis of DEFB1 haplotypes did not highlight any association of the three SNPs with AD development or disease severity.

CONCLUSIONS: Our results seem to exclude a role for the -44 C/G DEFB1 SNPs on the pathogenesis and severity of AD, while for the -20 C/G and -52 G/A, even if not statistically significant, we evidenced a slight trend for susceptibility (-20 GG) and protection (-52 GG) for the development of AD. However, as controversial findings have been reported in the literature, the role of DEFB1 in the development of AD and in the severity of the phenotype deserves further investigation.

}, keywords = {Adolescent, beta-Defensins, Brazil, Child, Child, Preschool, Dermatitis, Atopic, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Humans, Infant, Male, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1365-4632}, doi = {10.1111/j.1365-4632.2009.04343.x}, author = {Segat, Ludovica and Guimar{\~a}es, Rafael L and Brand{\~a}o, Lucas A C and Rocha, Cintia R C and Zanin, Valentina and Trevisiol, Chiara and de Lima Filho, Jos{\'e} Luiz and Crovella, Sergio} } @article {1683, title = {Histatins in non-human primates: gene variations and functional effects.}, journal = {Protein Pept Lett}, volume = {17}, year = {2010}, month = {2010 Jul}, pages = {909-18}, abstract = {

Human histatins are histidine-rich, low molecular weight salivary proteins that contribute to the immune system of the oral cavity. In this work, nucleotide sequences of the HIS1 (coding for histatin 1) and HIS2 (coding for histatin 3) genes, homologous to the human ones, have been sequenced and analysed in five primates species including Great Ape, Hylobatidae and Cercopithecidae. In HIS1, the region corresponding to the putative mature peptide shows a premature stop codon in Macaca and Cercopithecus, while HIS2 a six codon insertion in the Cercopithecidae. Histatin 5, a 24-residue peptide derived from histatin 3, is the most antimicrobially active among human histatins, thus macaque and nomascus orthologues of histatin 5 were selected for chemical synthesis and functional characterization, in comparison to the human peptide. All synthesized histatins are predicted to be poorly amphipathic, depending on the charged state of His residues and assume partially a-helical conformations only in lipophilic conditions. Antimicrobial assays against Candida and Criptococcus spp. indicate somewhat different spectra of in vitro activity against the tested fungi. We have described HIS1 and HIS2 gene variations in primates and have analysed their functional effects on selected Hst5 orthologues. The human antimicrobial peptide has been proposed to represent an important lead for new generation of antimicrobial compounds for the treatment of oral mycoses, thus the information from the non-human primates histatins studied may aid strategies for drugs design.

}, keywords = {Amino Acid Sequence, Animals, Anti-Infective Agents, Base Sequence, Candida, Catarrhini, Cell Proliferation, Computational Biology, Cryptococcus, Genetic Variation, Histatins, Humans, Molecular Sequence Data, Phylogeny, Sequence Alignment, Sequence Analysis, DNA}, issn = {1875-5305}, author = {Padovan, Lara and Segat, Ludovica and Pontillo, Alessandra and Antcheva, Nikolinka and Tossi, Alessandro and Crovella, Sergio} } @article {1700, title = {HLA-G*0105N allele is associated with augmented risk for HIV infection in white female patients.}, journal = {AIDS}, volume = {24}, year = {2010}, month = {2010 Jul 31}, pages = {1961-4}, abstract = {

We analyzed HLA-G 3777G > C, HLA-G 14 bp deletion/insertion and HLA-G*0105N polymorphisms in HIV-positive white adult participants, infected through horizontal heterosexual transmission, and unexposed uninfected individuals, all from north eastern Italy. We report a new association between the HLA-G*0105N allele and HIV infection in adult white female participants, being HLA-G*0105N null allele correlated with an augmented risk (odds ratio = 4.35, 95\% confidence interval = 1.38-18.07, P = 0.005) for HIV infection.

}, keywords = {Adolescent, Adult, Aged, Female, Genetic Predisposition to Disease, Histocompatibility Antigens Class I, HIV Infections, HIV-1, Humans, Middle Aged, Polymorphism, Genetic, Young Adult}, issn = {1473-5571}, doi = {10.1097/QAD.0b013e32833c3324}, author = {Segat, Ludovica and Catamo, Eulalia and Fabris, Annalisa and Morgutti, Marcello and D{\textquoteright}Agaro, Pierlanfranco and Campello, Cesare and Crovella, Sergio} }