A whole-genome association study of major determinants for host control of HIV-1

Abstract

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.

Fig. 1

HIV-1 VL at the set point is highly correlated with (A) the HCP5 rs2395029 genotype, where T is the major allele and G is the minor allele, and with (B) the HLA-C 5′ region rs9264942 genotype, where T is the major allele and C is the minor allele. Mean and SEM (error bars) are represented for the respective genotypes.

Fig. 2

Partial map of the HLA class I region (chromosome 6 p21.3). The P values [−log(P)] of all genotyped SNPs annotated with the gene structure are indicated. The two independent SNPs that show genome-wide significant association with HIV-1 VL at the set point are marked in red. The graph was drawn with WGAViewer software (www.genome.duke.edu/centers/pg2/index_html/downloads/AnnotationSoftware).