Functionally active HLA-G polymorphisms are associated with the risk of heterosexual HIV-1 infection in African women
| Autor: | Julie Lacaille, Michel Roger, Julie Lajoie, Lynn S. Zijenah, Brian J. Ward, Claudine Matte |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cellular immunity
Immunology Population HIV Infections Biology Acquired immunodeficiency syndrome (AIDS) Gene Frequency HLA Antigens Immunopathology Genotype medicine Immunology and Allergy Humans Genetic Predisposition to Disease education Heterosexuality Developing Countries HLA-G Antigens education.field_of_study Polymorphism Genetic Risk of infection Histocompatibility Antigens Class I Odds ratio medicine.disease Infectious Diseases HIV-1 Population study Female |
| Zdroj: | AIDS (London, England). 18(3) |
| ISSN: | 0269-9370 |
| Popis: | 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. (authors) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|