The HLA-B/-C haplotype block contains major determinants for host control of HIV

A genome-wide association study of people with incident human immunodeficiency virus (HIV) infection selected from nine different cohorts identified allelic polymorphisms, which associated with either viral set point (HCP5 and 5' HLA-C) or with HIV disease progression (RNF39 and ZNRD1). To determine the influence of these polymorphisms on host control of HIV, we carried out a population-based association study. The analysis revealed complete linkage disequilibrium between HCP5 and HLA-B* 5701/HLA-Cw* 06, a modest effect of 5' HLA-C on viral set point in the absence of HLA-B* 5701, and no influence of the RNF39 /ZNRD1 extended haplotype on HIV disease progression. No correlation was found between the infection status and any of these genetic variants (P>0.1, Fisher's exact test). These findings suggest a pattern of strong linkage disequilibrium consistent with an HLA-B/-C haplotype block, making identification of a causal variant difficult, and underscore the importance of validating polymorphisms in putative determinants for host control by association analysis of independent populations. Genes and Immunity (2009) 10, 673-677; doi: 10.1038/gene.2009.58; published online 20 August 2009