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

Abstract

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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.

Citation

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To cite this publication, please use the following BibTeX entry:

@article{ekenbergAssociationSingleNucleotidePolymorphisms2019,
  author = {Ekenberg, Christina and Tang, Man-Hung and Zucco, Adrian G. and Murray, Daniel D. and MacPherson, Cameron Ross and Hu, Xiaojun and Sherman, Brad T. and Losso, Marcelo H. and Wood, Robin and Paredes, Roger and Molina, Jean-Michel and Helleberg, Marie and Jina, Nureen and Kityo, Cissy M. and Florence, Eric and Polizzotto, Mark N. and Neaton, James D. and Lane, H. Clifford and Lundgren, Jens D.},
  doi = {10.1093/infdis/jiz294},
  issn = {0022-1899},
  journal = {The Journal of Infectious Diseases},
  langid = {english},
  month = {September},
  number = {8},
  pages = {1325--1334},
  title = {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},
  urldate = {2019-10-21},
  volume = {220},
  year = {2019}
}