Association between single-nucleotide polymorphisms in HLA alleles and human immunodeficiency virus type 1 viral load in demographically diverse, antiretroviral therapy-naive participants from the strategic timing of antiRetroviral treatment trial

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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 log(10) 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.

Original languageEnglish
JournalJournal of Infectious Diseases
Volume220
Issue number8
Pages (from-to)1325-1334
Number of pages10
ISSN0022-1899
DOIs
Publication statusPublished - 2019

Keywords

  • HIV-1
  • host genetics
  • genome-wide association study
  • GWAS
  • viral load
  • HLA
  • HIV-1 INFECTION
  • DISEASE PROGRESSION
  • GENETIC RESTRICTION
  • CHEMOKINE RECEPTOR
  • AIDS
  • DETERMINANTS
  • INDIVIDUALS
  • EXPRESSION
  • RESISTANCE
  • ADVANTAGE

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