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

J. Lane; P.J. McLaren; L. Dorrell; K.V. Shianna; A. Stemke; K. Pelak; S. Moore; J. Oldenburg; F. Boehlen; B. Brand; D. Brown; E. Chiang; B. Clotet; P. Collins; S. Colombo; J. Dalmau; P. Fogarty; P. Giangrande; A. Gringeri; R. Iyer; O. Katsarou; C. Kempton; P. Kuriakose; J. Lin; M. Makris; D.A. Tsakiris; A. Neff; S. Oka; L. Oyesiku; R. Parra; J. Powell; M. Recht; A. Shapiro; K. Stine; K. Talks; A. Telenti; J. Wilde; T.T. Yee; S.M. Wolinsky; J. Martinson; S.K. Hussain; J.H. Bream; L.P. Jacobson; M. Carrington; J.J. Goedert; B.F. Haynes; A.J. McMichael; D.B. Goldstein; J. Fellay

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

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Auteurs

Date

2013

Type de document

Articles

Périmètre

Publications

Langue

Anglais

Identifiants

doi: 10.1093/hmg/ddt033
issn: 0964-6906

Source

Serveur académique Lausannois

Relations

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1093/hmg/ddt033

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/23372042

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1460-2083

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_274A16CCE4105

Collection

Serveur Académique Lausannois

Organisation

Université de Lausanne et CHUV

Licences

info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

Sujets proches En

Haemophilia Hematophilia Classic hemophilia Factor VIII deficiency Hemophilia A Hemorrhagic diathesis

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J. Lane et al., « A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. », Serveur académique Lausannois, ID : 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.

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

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