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A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Lane Jérôme, McLaren Paul J, Dorrell Lucy, Shianna Kevin V, Stemke Amanda, Pelak Kimberly, Moore Stephen, Oldenburg Johannes, Alvarez-Roman Maria Teresa, Angelillo-Scherrer Anne, Boehlen Francoise, Bolton-Maggs Paula H B, Brand Brigit, Brown Deborah, Chiang Elaine, Cid-Haro Ana Rosa, Clotet Bonaventura, Collins Peter, Colombo Sara, Dalmau Judith, Fogarty Patrick, Giangrande Paul, Gringeri Alessandro, Iyer Rathi, Katsarou Olga,
Project Host evolutionary genomics of HIV-1 and other retroviruses
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Original article (peer-reviewed)

Journal Human molecular genetics
Volume (Issue) 22(9)
Page(s) 1903 - 10
Title of proceedings Human molecular genetics
DOI 10.1093/hmg/ddt033

Abstract

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.
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