Evidence after imputation for a role of MICA variants in nonprogression and elite control of HIV type 1 infection

J Infect Dis. 2014 Dec 15;210(12):1946-50. doi: 10.1093/infdis/jiu342. Epub 2014 Jun 16.

Abstract

Past genome-wide association studies (GWAS) involving individuals with AIDS have mainly identified associations in the HLA region. Using the latest software, we imputed 7 million single-nucleotide polymorphisms (SNPs)/indels of the 1000 Genomes Project from the GWAS-determined genotypes of individuals in the Genomics of Resistance to Immunodeficiency Virus AIDS nonprogression cohort and compared them with those of control cohorts. The strongest signals were in MICA, the gene encoding major histocompatibility class I polypeptide-related sequence A (P = 3.31 × 10(-12)), with a particular exonic deletion (P = 1.59 × 10(-8)) in full linkage disequilibrium with the reference HCP5 rs2395029 SNP. Haplotype analysis also revealed an additive effect between HLA-C, HLA-B, and MICA variants. These data suggest a role for MICA in progression and elite control of human immunodeficiency virus type 1 infection.

Keywords: AIDS; GWAS; HIV-1; MICA; SNP; elite control; imputation; indel; non progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Disease Resistance*
  • Female
  • Genetic Association Studies
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Linkage Disequilibrium
  • Major Histocompatibility Complex / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Young Adult

Substances

  • HCP5 long noncoding RNA, human
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • RNA, Long Noncoding
  • RNA, Untranslated