Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS genomewide association study 02)

Sophie Limou, Sigrid Le Clerc, Cédric Coulonges, Wassila Carpentier, Christian Dina, Olivier Delaneau, Taoufik Labib, Lieng Taing, Rob Sladek, Christiane Deveau, Rojo Ratsimandresy, Matthieu Montes, Jean Louis Spadoni, Jean Daniel Lelièvre, Yves Lévy, Amu Therwath, François Schächter, Fumihiko Matsuda, Ivo Gut, Philippe FroguelJean François Delfraissy, Serge Hercberg, Jean François Zagury*, Laurence Meyer, Philippe Broët, Cyril Dalmasso, Patrice Debré, Ioannis Théodorou, Christine Rouzioux

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

185 Scopus citations

Abstract

To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5rs2395029 (P = 6.79 × 10-10; odds ratio, 3.47) and was possibly linked to an effect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P = 3.02 × 10-19) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.

Original languageEnglish (US)
Pages (from-to)419-426
Number of pages8
JournalJournal of Infectious Diseases
Volume199
Issue number3
DOIs
StatePublished - Feb 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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