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


Autoria(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.; NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
Data(s)

2013

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_274A16CCE410

isbn:1460-2083 (Electronic)

pmid:23372042

doi:10.1093/hmg/ddt033

isiid:000317431100019

Idioma(s)

en

Fonte

Human Molecular Genetics, vol. 22, no. 9, pp. 1903-1910

Tipo

info:eu-repo/semantics/article

article