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Functionally active HLA-G polymorphisms are associated with the risk of heterosexual HIV-1 infection in African women

Matte, Claudinea,b; Lajoie, Juliea,b; Lacaille, Juliea; Zijenah, Lynn Sc; Ward, Brian Jd; Roger, Michela,b

Basic Science: Concise Communications

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.

From the aLaboratory of Immunogenetics, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal General Hospital Research Institute and the bDepartment of Microbiology and Immunology, Montréal University, Montréal, Canada, the cDepartment of Immunology, University of Zimbabwe, Harare, Zimbabwe and the dResearch Institute of the McGill University Hospital Complex, Montréal, Canada.

Correspondence to Dr M. Roger, Département de microbiologie, Hôpital Notre-Dame du CHUM, 1560 Sherbrooke Est, Montréal, Québec, Canada H2L 4M1.

Received: 22 May 2003; revised: 7 July 2003; accepted: 15 July 2003.

© 2004 Lippincott Williams & Wilkins, Inc.