Functionally active HLA-G polymorphisms are associated with the risk of heterosexual HIV-1 infection in African women
Matte, C.; Lajoie, J.; Lacaille, J.; Zijenah, L.S.; Ward, B.J.; Roger, M.
Aids 18(3): 427-431
2004
ISSN/ISBN: 0269-9370 PMID: 15090794 DOI: 10.1097/00002030-200402200-00008Document Number: 232851
Background: Heterosexual transmission of HIV-1 is the major route of infection worldwide. HLA-G molecules are involved in the inhibition of cell-mediated immune responses and could permit or even promote the propagation of infection in the female reproductive tract. Objective: To examine whether HLA-G genetic variants are associated with the risk of heterosexual HIV-1 infection. Methods: HLA-G polymorphism in DNA samples from 431 (228 HIV-positive and 203 HIV-negative) Zimbabwean women was determined by amplified-restriction fragment length polymorphism and DNA sequencing analyses. Results: Six HLA-G alleles were identified in the study population. HLA-G*0105N, which does not encode functional HLA-G1 proteins, was significantly associated with protection from HIV-1 infection (odds ratio (OR), 0.51; 95% confidence interval (CI), 0.31-0.85; P = 0.0083). The HLA-G*010108 allele was associated with a 2.5-fold increased risk of HIV-1 infection (OR, 2.47; 95% CI, 1.32-4.64; P = 0.0038). In addition, two HLA-G*010108-containing genotypes were associated with elevated risk of HIV-1 infection: HLA-G*010108/010401 (OR, 23.6; 95% CI, 1.39-401.7; P = 0.0009) and G*010101/010108 (OR, 5.6; 95% CI, 1.24-25.3; P = 0.012). Conclusion: This study demonstrates that functionally active HLA-G polymorphisms are associated with altered risk of HIV-1 infection in African women. This provides evidence to support the hypothesis that modulation of HLA-G expression by HIV-1 can contribute to the risk of infection. Targeted interventions to reduce or block HLA-G expression in genital tissues could lead to novel strategies for the prevention of heterosexual HIV-1 transmission.