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


CONCLUSIONS
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.
Matte
Claudine
C
Laboratory of Immunogenetics, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal General Hospital Research Institute, Montréal, Canada.
Lajoie
Julie
J
Lacaille
Julie
J
Zijenah
Lynn S
LS
Ward
Brian J
BJ
Roger
Michel
M
D003906:Developing Countries; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics / Q000635:transmission*; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D020010:Heterosexuality; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I