Details

Autor(en) / Beteiligte

• Limou, Sophie
• Delaneau, Olivier
• van Manen, Daniëlle
• An, Ping
• Sezgin, Efe
• Le Clerc, Sigrid
• Coulonges, Cédric
• Troyer, Jennifer L.
• Veldink, Jan H.
• van den Berg, Leonard H.
• Spadoni, Jean-Louis
• Taing, Lieng
• Labib, Taoufik
• Montes, Matthieu
• Delfraissy, Jean-François
• Schachter, François
• O'Brien, Stephen J.
• Buchbinder, Susan
• van Natta, Mark L.
• Jabs, Douglas A.
• Froguel, Philippe
• Schuitemaker, Hanneke
• Winkler, Cheryl A.
• Zagury, Jean-François

Titel

Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition

Ist Teil von

• The Journal of infectious diseases, 2012-04, Vol.205 (7), p.1155-1162

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10⁻⁵ in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T alíele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: P combined = 7.76 X 10⁻⁸. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.