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

Details

Ressource 1Download: serval:BIB_274A16CCE410.P001 (143.43 [Ko])
State: Public
Version: author
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_274A16CCE410
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.
Journal
Human Molecular Genetics
Author(s)
Lane J., McLaren P.J., Dorrell L., Shianna K.V., Stemke A., Pelak K., Moore S., Oldenburg J., Alvarez-Roman M.T., Angelillo-Scherrer A., Boehlen F., Bolton-Maggs P.H., Brand B., Brown D., Chiang E., Cid-Haro A.R., Clotet B., Collins P., Colombo S., Dalmau J., Fogarty P., Giangrande P., Gringeri A., Iyer R., Katsarou O., Kempton C., Kuriakose P., Lin J., Makris M., Manco-Johnson M., Tsakiris D.A., Martinez-Picado J., Mauser-Bunschoten E., Neff A., Oka S., Oyesiku L., Parra R., Peter-Salonen K., Powell J., Recht M., Shapiro A., Stine K., Talks K., Telenti A., Wilde J., Yee T.T., Wolinsky S.M., Martinson J., Hussain S.K., Bream J.H., Jacobson L.P., Carrington M., Goedert J.J., Haynes B.F., McMichael A.J., Goldstein D.B., Fellay J.
Working group(s)
NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
2013
Volume
22
Number
9
Pages
1903-1910
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
16/05/2013 17:48
Last modification date
25/09/2019 7:08
Usage data