Influence of HLA-G Polymorphisms In Human Immunodeficiency Virus Infection and hepatitis C Virus Co-Infection in Brazilian and Italian Individuals

Objective: This study aimed to investigate the role of Human Leukocyte Antigen (HLA)-G in the susceptibility to HIV-1 infection through the analysis of the HLA-G 30 untranslated region (UTR) polymorphisms 14 bp insertion/deletion (rs66554220) and +3142C>G (rs1063320). Design: We analyzed 582 HIV-1 infected patients and 626 uninfected individuals from Brazil and Italy in a case-control study. Methods: HLA-G polymorphisms were genotyped using PCR, PCR-RFLP assays or direct sequencing. All analyses were stratified by ethnicity. Genotypic, allelic and diplotypic frequencies were compared between HIV-1 infected subjects and controls using Chi-square or Fischer exact tests. Also, haplotypic frequencies were estimated using MLocus software. Results: African-derived HIV-infected individuals presented a higher frequency of the 14 bp insertion allele as compared to non-infected individuals (0.468 versus 0.373, respectively; pBonf = 0.010). A higher frequency of the 14 bp insertion +3142G (insG) haplotype (0.456 versus 0.346, p < 0.001) and the insG/ insG diplotype (OR = 1.88, 95%CI = 1.08–3.23, p = 0.021) was observed among African-derived patients as compared to uninfected controls. Also, we observed a higher frequency of the ins/ins genotype among African-derived HIV patients co-infected with HCV (OR = 2.78, 95%CI = 1.20–6.49, p = 0.008). Conclusions: Our data point out to an increased frequency of alleles and genotypes associated with low HLA-G expression among African-derived patients, suggesting a potential role for HLA-G in the susceptibility to HIV-1 infection and HCV co-infection in those individuals.