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.
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: Heather A Hong; Maria Paximadis; Glenda E Gray; Louise Kuhn; Caroline T Tiemessen Journal: Infect Genet Evol Date: 2014-12-23 Impact factor: 3.342
Authors: Giorgio Sirugo; Branwen J Hennig; Adebowale A Adeyemo; Alice Matimba; Melanie J Newport; Muntaser E Ibrahim; Kelli K Ryckman; Alessandra Tacconelli; Renato Mariani-Costantini; Giuseppe Novelli; Himla Soodyall; Charles N Rotimi; Raj S Ramesar; Sarah A Tishkoff; Scott M Williams Journal: Hum Genet Date: 2008-05-30 Impact factor: 4.132
Authors: Mary B Cauldbeck; Catherine O'Connor; Mortimer B O'Connor; Jean A Saunders; Bhimasena Rao; V G Mallesh; Nagendrappa Kotehalappa Praveen Kumar; Gurushanthappa Mamtha; Claire McGoldrick; Robert Bs Laing; Kadappa Shivappa Satish Journal: AIDS Res Ther Date: 2009-04-28 Impact factor: 2.250