@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 {3518, title = {Block of the mevalonate pathway triggers oxidative and inflammatory molecular mechanisms modulated by exogenous isoprenoid compounds.}, journal = {Int J Mol Sci}, volume = {15}, year = {2014}, month = {2014}, pages = {6843-56}, abstract = {

Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD). One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines{\textquoteright} release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3), cytokines and nitric oxide (NO)]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.

}, keywords = {Animals, Apoptosis, Carotenoids, Carrier Proteins, Cell Line, Cytokines, Diterpenes, Humans, Mevalonate Kinase Deficiency, Mevalonic Acid, Mice, Mitochondria, Nitric Oxide, Phytol, Terpenes}, issn = {1422-0067}, doi = {10.3390/ijms15046843}, author = {Tricarico, Paola Maura and Kleiner, Giulio and Valencic, Erica and Campisciano, Giuseppina and Girardelli, Martina and Crovella, Sergio and Knowles, Alessandra and Marcuzzi, Annalisa} } @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} }