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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.

Original publication

DOI

10.1093/hmg/ddt033

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/05/2013

Volume

22

Pages

1903 - 1910

Keywords

Adult, DNA Copy Number Variations, Disease Resistance, Epistasis, Genetic, Factor VIII, Female, Gene Deletion, Genetic Predisposition to Disease, Genome-Wide Association Study, HIV Infections, HIV Seropositivity, Hemophilia A, Heterozygote, Homozygote, Humans, Logistic Models, Male, Meta-Analysis as Topic, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Receptors, CCR5