Journal
HUMAN MOLECULAR GENETICS
Volume 22, Issue 9, Pages 1903-1910Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt033
Keywords
-
Funding
- National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI067854]
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Intramural Research Program of the National Institutes of Health
- Frederick National Lab
- Center for Cancer Research
- National Institute of Allergy and Infectious Diseases
- National Cancer Institute [UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI35040, UO1-AI-35041]
- Medical Research Council [MR/K012037/1] Funding Source: researchfish
- MRC [MR/K012037/1] Funding Source: UKRI
Ask authors/readers for more resources
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 D32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4) were homozygous for CCR5 32 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available