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

Publication ,  Journal Article
Lane, J; McLaren, PJ; Dorrell, L; Shianna, KV; Stemke, A; Pelak, K; Moore, S; Oldenburg, J; Alvarez-Roman, MT; Angelillo-Scherrer, A; Brand, B ...
Published in: Hum Mol Genet
May 1, 2013

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.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

May 1, 2013

Volume

22

Issue

9

Start / End Page

1903 / 1910

Location

England

Related Subject Headings

  • Receptors, CCR5
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Logistic Models
  • Humans
  • Homozygote
 

Citation

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Lane, J., McLaren, P. J., Dorrell, L., Shianna, K. V., Stemke, A., Pelak, K., … NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI), . (2013). A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Hum Mol Genet, 22(9), 1903–1910. https://doi.org/10.1093/hmg/ddt033
Lane, Jérôme, Paul J. McLaren, Lucy Dorrell, Kevin V. Shianna, Amanda Stemke, Kimberly Pelak, Stephen Moore, et al. “A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.Hum Mol Genet 22, no. 9 (May 1, 2013): 1903–10. https://doi.org/10.1093/hmg/ddt033.
Lane J, McLaren PJ, Dorrell L, Shianna KV, Stemke A, Pelak K, et al. A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Hum Mol Genet. 2013 May 1;22(9):1903–10.
Lane, Jérôme, et al. “A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.Hum Mol Genet, vol. 22, no. 9, May 2013, pp. 1903–10. Pubmed, doi:10.1093/hmg/ddt033.
Lane J, McLaren PJ, Dorrell L, Shianna KV, Stemke A, Pelak K, Moore S, Oldenburg J, Alvarez-Roman MT, Angelillo-Scherrer A, Boehlen F, Bolton-Maggs PHB, Brand B, Brown D, Chiang E, Cid-Haro AR, 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 DA, 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 TT, Wolinsky SM, Martinson J, Hussain SK, Bream JH, Jacobson LP, Carrington M, Goedert JJ, Haynes BF, McMichael AJ, Goldstein DB, Fellay J, NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Hum Mol Genet. 2013 May 1;22(9):1903–1910.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

May 1, 2013

Volume

22

Issue

9

Start / End Page

1903 / 1910

Location

England

Related Subject Headings

  • Receptors, CCR5
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Logistic Models
  • Humans
  • Homozygote