Genetic associations of variants in genes encoding HIV-dependency factors required for HIV-1 infection

J Infect Dis. 2010 Dec 15;202(12):1836-45. doi: 10.1086/657322.

Abstract

Background: High-throughput genome-wide techniques have facilitated the identification of previously unknown host proteins involved in cellular human immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used small interfering RNA technology to silence each gene in the human genome to determine the importance of each in HIV infection. Genes conferring a significant effect were termed HIV-dependency factors (HDFs).

Methods: We assembled high-density panels of 6380 single-nucleotide polymorphisms (SNPs) in 278 HDF genes and tested for genotype associations with HIV infection and AIDS progression in 1633 individuals from clinical AIDS cohorts.

Results: After statistical correction for multiple tests, significant associations with HIV acquisition were found for SNPs in 2 genes, NCOR2 and IDH1. Weaker associations with AIDS progression were revealed for SNPs within the TM9SF2 and EGFR genes.

Conclusions: This study independently verifies the influence of NCOR2 and IDH1 on HIV transmission, and its findings suggest that variation in these genes affects susceptibility to HIV infection in exposed individuals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Disease Progression
  • Disease Susceptibility*
  • ErbB Receptors / genetics
  • Gene Frequency
  • HIV Infections / genetics*
  • HIV Infections / transmission*
  • HIV-1 / pathogenicity*
  • Host-Pathogen Interactions*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Membrane Proteins / genetics
  • Nuclear Receptor Co-Repressor 2 / genetics*
  • Polymorphism, Single Nucleotide

Substances

  • Membrane Proteins
  • NCOR2 protein, human
  • Nuclear Receptor Co-Repressor 2
  • TM9SF2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • EGFR protein, human
  • ErbB Receptors

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