Genetic Variants in Nonclassical Major Histocompatibility Complex Class I Human Leukocyte Antigen (HLA)–E and HLA‐G Molecules Are Associated with Susceptibility to Heterosexual Acquisition of HIV‐1

Abstract
Human leukocyte antigen (HLA)–E and HLA-G molecules act as powerful modulators of the innate immune response. The present study shows that the HLA-EG genetic variant (the HLA-E*0103 allele) alone is significantly (P=.001) associated with a 4.0-fold decreased risk of human immunodeficiency virus 1 (HIV-1) infection in Zimbabwean women. Furthermore, women carrying the combination of the protective HLA-EG homozygote and HLA-G*0105N heterozygote genotypes had a 12.5-fold decreased risk of HIV-1 infection (P=.03), compared with women carrying neither genotype. These associations remained significant after adjustment was made for other significant sociodemographic risk factors for HIV prevalence in this population. In conclusion, HLA-E and HLA-G polymorphisms can independently and synergistically influence susceptibility to heterosexual acquisition of HIV-1

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