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

Lane, Jérôme; McLaren, Paul J.; Dorrell, Lucy; Shianna, Kevin V.; Stemke, Amanda; Pelak, Kimberly; Moore, Stephen; Oldenburg, Johannes; Boehlen, Francoise; Alvarez-Roman, Maria Teresa; Angelillo-Scherrer, Anne; Bolton-Maggs, Paula H. B.; Brand, Brigit; Brown, Deborah; Chiang, Elaine; Cid-Haro, Ana Rosa; Clotet, Bonaventura; Collins, Peter; Colombo, Sara; Dalmau, Judith; ... (2013). A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Human molecular genetics, 22(9), pp. 1903-1910. Oxford University Press 10.1093/hmg/ddt033

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Angelillo, Anne

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0964-6906

Publisher:

Oxford University Press

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

18 Jul 2014 08:07

Last Modified:

27 Apr 2018 08:45

Publisher DOI:

10.1093/hmg/ddt033

PubMed ID:

23372042

BORIS DOI:

10.7892/boris.47388

URI:

https://boris.unibe.ch/id/eprint/47388

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