Association between single-nucleotide polymorphisms in HLA alleles and human immunodeficiency virus type 1 viral load in demographically diverse, antiretroviral …

C Ekenberg, MH Tang, AG Zucco… - The Journal of …, 2019 - academic.oup.com
The Journal of infectious diseases, 2019academic.oup.com
The impact of variation in host genetics on replication of human immunodeficiency virus type
1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we
performed a genome-wide screen for associations of single-nucleotide polymorphisms
(SNPs) to viral load (VL) in antiretroviral therapy–naive participants (n= 2440) with varying
demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial.
Associations were assessed using genotypic data generated by a customized SNP array …
Abstract
The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy–naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed HLA alleles, and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex class I region (MHC I), with effect sizes ranging between 0.14 and 0.39 log10 VL (copies/mL). Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the (MHC I) is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of genome-wide association studies as being merely a screening tool.
Oxford University Press