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) |
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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: |
20 Dec 2022 12:49 |
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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