@article {10459, title = {HLA-G regulatory polymorphisms are associated with susceptibility to HCV infection.}, journal = {HLA}, volume = {89}, year = {2017}, month = {2017 03}, pages = {135-142}, abstract = {

BACKGROUND: Hepatitis C virus (HCV) is able to bypass the immune system modulating innate and adaptive immune response and blocking T helper 1 (Th1) cell production. Because the human leukocyte antigen (HLA)-G molecule has immunomodulatory properties inhibiting the function and production of natural killer and cytotoxic lymphocyte T cells, as well as promoting shift from Th1 toward Th2 response, we hypothesized its involvement in susceptibility to HCV infection.

MATERIALS AND METHODS: Considering that HLA-G mRNA expression has been reported to be under genetic control, an association study was conducted analyzing 800 base pairs upstream the ATG at the 5{\textquoteright}upstream regulator region (URR) and 850 base pairs from ATG to exon 3 and the 3{\textquoteright}untranslated region (UTR) of HLA-G gene in Italian HCV-positive patients and uninfected controls.

RESULTS: Four 5{\textquoteright}URR polymorphisms (-725C>G>T, -509C>G, -400G>A and -398G>A), 7 polymorphisms at coding region (+15G>A, +36G>A, +243G>A, insC506, 531G>C, delA615 and 685G>A), the +644G>T polymorphism, and 1 haplotype (TTGTTCCIGAC) showed different frequency distributions between HCV patients and uninfected controls.

CONCLUSION: The results from our study suggest a possible involvement of HLA-G in the risk modulation toward HCV infection.

}, keywords = {3{\textquoteright} Untranslated Regions, 5{\textquoteright} Untranslated Regions, Adult, Aged, Aged, 80 and over, Alleles, Case-Control Studies, Exons, Female, Gene Expression, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Haplotypes, Hepacivirus, Hepatitis C, HLA-G Antigens, Humans, Italy, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Th1 Cells}, issn = {2059-2310}, doi = {10.1111/tan.12959}, author = {Catamo, E and Zupin, L and Freato, N and Polesello, V and Celsi, F and Croc{\`e}, S L and Masutti, F and Pozzato, G and Segat, L and Crovella, S} } @article {8291, title = {Association of the HLA-G 3{\textquoteright}UTR polymorphisms with colorectal cancer in Italy: a first insight.}, journal = {Int J Immunogenet}, volume = {43}, year = {2016}, month = {2016 Feb}, pages = {32-9}, abstract = {

This study aimed to explore functional and regulatory polymorphisms and haplotypes at the HLA-G 3{\textquoteright}UTR region in colorectal cancer development. The presence of nonpolymorphic variants was also evaluated. Three-hundred and eight patients with colorectal cancer and 294 healthy controls were analysed at the germinal level. We found an association with increased risk of colorectal cancer for +2960 14-bp INDEL, +3196 C>G SNPs and UTR-2 haplotype, and a {\textquoteright}protective{\textquoteright} role for +3003 T>C, +3010 C>G polymorphisms and UTR-4 haplotype. We detected in 3 distinct patients, a novel nucleotide change (+3037 C>A) and 2 already described rare variants, +3032 G/C (EUR MAF~=~0.1\%) and +3092~G/T (EUR MAF~=~0\%). This is the first study showing associations between different polymorphisms in the HLA-G 3{\textquoteright}UTR and colorectal cancer susceptibility.

}, issn = {1744-313X}, doi = {10.1111/iji.12243}, author = {Garziera, M and Catamo, E and Crovella, S and Montico, M and Cecchin, E and Lonardi, S and Mini, E and Nobili, S and Romanato, L and Toffoli, G} } @article {7753, title = {Comprehensive analysis of polymorphisms in the HLA-G 5{\textquoteright} upstream regulatory and 3{\textquoteright} untranslated regions in Brazilian patients with systemic lupus erythematosus.}, journal = {Tissue Antigens}, volume = {85}, year = {2015}, month = {2015 Jun}, pages = {458-65}, abstract = {

This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5{\textquoteright} upstream regulatory region (URR), 3{\textquoteright} untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12\% in SLE patients vs 6\% in controls; odds ratio (OR), 2.10, 95\% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8\% in SLE patients and 6.3\% in controls; OR, 2.14, 95\% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is far from being elucidated yet, our association study results along with a systematic review and meta-analysis suggest that HLA-G might be able to slightly modulate the complex SLE phenotype (pooled OR, 1.14, 95\% CI, 1.02-1.27, P = 0.021).

}, issn = {1399-0039}, doi = {10.1111/tan.12545}, author = {Catamo, E and Addobbati, C and Segat, L and Sotero Fragoso, T and Tavares Dantas, A and de Ata{\'\i}de Mariz, H and Ferreira da Rocha Junior, L and Branco PintoDuarte, A L and Coelho, A V C and de Moura, R R and Polesello, V and Crovella, S and Sandrin Garcia, P} } @article {3504, title = {HLA-G 14 bp deletion/insertion polymorphism and mother-to-child transmission of HIV.}, journal = {Tissue Antigens}, volume = {83}, year = {2014}, month = {2014 Mar}, pages = {161-7}, abstract = {

The human leukocyte antigen HLA-G, highly expressed at the maternal-fetal interface, has a pivotal role in mediating immune tolerance. In this study we investigated the influence of HLA-G 14 bp insertion polymorphism in human immunodeficiency virus (HIV)-1 mother-to-child HIV-1 transmission. The 14 bp insertion polymorphism was analyzed among 99 HIV-1 positive mothers and 329 infants born to HIV-positive mothers in Zambia, among whom vertical transmission status and timing had been determined. HLA-G 14 bp insertion polymorphism was detected using a custom TaqMan single nucleotide polymorphisms (SNPs) genotyping assay. Logistic regression was conducted to examine the associations between HLA-G alleles and the risk of HIV transmission. The 14 bp insertion allele was more frequent in HIV exposed-uninfected (EU) infants than in infected infants, and was associated with reduced risk of both in utero (IU) and intrapartum (IP) HIV transmission, after adjusting for maternal cluster of differentiation 4 (CD4) cell count and plasma viral load. Maternal HLA-G 14 bp insertion genotype and HLA-G concordance between mother and child were not associated with the risk of perinatal HIV transmission. The presence of the 14 bp insertion associates with protection toward IU and IP HIV infection in children from Zambia, suggesting that HLA-G could be involved in the vertical transmission of HIV.

}, keywords = {Adult, Alleles, Base Pairing, Child, Genotype, HIV Infections, HLA-G Antigens, Humans, INDEL Mutation, Infant, Infectious Disease Transmission, Vertical, Mothers, Polymorphism, Genetic, Young Adult}, issn = {1399-0039}, doi = {10.1111/tan.12296}, author = {Segat, L and Zupin, L and Kim, H-Y and Catamo, E and Thea, D M and Kankasa, C and Aldrovandi, G M and Kuhn, L and Crovella, S} } @article {3567, title = {HLA-G gene polymorphisms associated with susceptibility to rheumatoid arthritis disease and its severity in Brazilian patients.}, journal = {Tissue Antigens}, volume = {84}, year = {2014}, month = {2014 Sep}, pages = {308-15}, abstract = {

We analyzed the possible association between human leukocyte antigen-G (HLA-G) genetic variants, supposed to regulate HLA-G expression, and the susceptibility to develop rheumatoid arthritis (RA) as well as its clinical manifestations. The 5{\textquoteright}upstream regulatory region (5{\textquoteright}URR) and 3{\textquoteright}untranslated region (3{\textquoteright}UTR) regions of the HLA-G gene were screened in 127 RA patients and 128 controls: 10 5{\textquoteright}URR and 3 3{\textquoteright}UTR HLA-G polymorphisms as well as two haplotypes were associated with risk for RA development, while a polymorphism in the 5{\textquoteright}URR showed an association with the degree of disease activity. These findings, although the number of cases analyzed is limited and the P-values are modest, indicate a possible association between HLA-G gene polymorphisms and susceptibility to develop RA disease and its severity.

}, keywords = {3{\textquoteright} Untranslated Regions, 5{\textquoteright} Flanking Region, Aged, Arthritis, Rheumatoid, Brazil, Disease Progression, DNA Mutational Analysis, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Haplotypes, HLA-G Antigens, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk}, issn = {1399-0039}, doi = {10.1111/tan.12396}, author = {Catamo, E and Addobbati, C and Segat, L and Sotero Fragoso, T and Domingues Barbosa, A and Tavares Dantas, A and de Ata{\'\i}de Mariz, H and F da Rocha, L and Branco Pinto Duarte, A L and Monasta, L and Sandrin-Garcia, P and Crovella, S} } @article {1880, title = {CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian patients.}, journal = {Genes Immun}, volume = {13}, year = {2012}, month = {2012 Sep}, pages = {489-95}, abstract = {

Celiac disease (CD) is a T-cell-mediated chronic inflammatory disease characterized by autoimmune, immunological and environmental components, where genetic factors in addition to the main known risk factors (gliadin and human leukocyte antigen (HLA)-DQ haplotypes) are supposed to be involved. CD14 is a multifunctional receptor involved in the bacterial lipopolysaccharides-dependent signal transduction. The CD14 gene maps on the long arm of chromosome 5 (5q22-q32), a {\textquoteright}hotbed{\textquoteright} region for CD; promoter polymorphisms are known to influence its expression. In this study we analyzed three CD14 promoter polymorphisms (c.-1359G>T, c.-1145A>G and c.-159C>T, ) in 938 CD Italian patients and 533 healthy controls, with known HLA-DQ haplotypes, with the aim of evaluating their possible association with the disease. The c.-1145A>G G and c.-159C>T T alleles (as well as the combination of the two alleles in the GT haplotype), were identified as susceptibility factors for CD development, being significantly more frequent in CD patients than in healthy controls. This association was also confirmed when the analysis was restricted to only those subjects characterized by HLA-DQ risk haplotypes. Our results indicate the involvement of CD14 gene polymorphisms in the susceptibility to CD.

}, keywords = {Adolescent, Adult, Aged, Antigens, CD14, Case-Control Studies, Celiac Disease, Child, Child, Preschool, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, HLA Antigens, Humans, Infant, Italy, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult}, issn = {1476-5470}, doi = {10.1038/gene.2012.23}, author = {Catamo, E and Segat, L and Lenarduzzi, S and Petix, V and Morgutti, M and Crovella, S} }