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The HLA-B/-C haplotype block contains major determinants for host control of HIV

Genes & Immunity volume 10, pages 673–677 (2009)Cite this article

Abstract

A genome-wide association study of people with incident human immunodeficiency virus (HIV) infection selected from nine different cohorts identified allelic polymorphisms, which associated with either viral set point (HCP5 and 5′ HLA-C) or with HIV disease progression (RNF39 and ZNRD1). To determine the influence of these polymorphisms on host control of HIV, we carried out a population-based association study. The analysis revealed complete linkage disequilibrium between HCP5 and HLA-B*5701/HLA-Cw*06, a modest effect of 5′ HLA-C on viral set point in the absence of HLA-B*5701, and no influence of the RNF39 /ZNRD1 extended haplotype on HIV disease progression. No correlation was found between the infection status and any of these genetic variants (P>0.1, Fisher's exact test). These findings suggest a pattern of strong linkage disequilibrium consistent with an HLA-B/-C haplotype block, making identification of a causal variant difficult, and underscore the importance of validating polymorphisms in putative determinants for host control by association analysis of independent populations.

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References

  1. Singh KK, Spector SA . Host genetic determinants of HIV infection and disease progression in children. Pediatr Res 2009. (electronic; Accession #19190524; ISSN 1530-0447).

  2. Piacentini L, Biasin M, Fenizia C, Clerici M . Genetic correlates of protection against HIV infection: the ally within. J Intern Med 2009; 265: 110–124.

    Article  CAS  Google Scholar 

  3. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317: 944–947.

    Article  CAS  Google Scholar 

  4. Trachtenberg E, Korber B, Sollars C, Kepler T, Hraber P, Hayes E et al. Advantage of rare HLA supertype in HIV disease progression. Nat Med 2003; 9: 928–935.

    Article  CAS  Google Scholar 

  5. Han Y, Lai J, Barditch-Crovo P, Gallant JE, Williams TM, Siliciano RF et al. The role of protective HCP5 and HLA-C associated polymorphisms in the control of HIV-1 replication in a subset of elite suppressors. AIDS 2008; 22: 541–544.

    Article  CAS  Google Scholar 

  6. Stranger BE, Forrest MS, Clark AG, Minichiello MJ, Deutsch S, Lyle R et al. Genome-wide associations of gene expression variation in humans. PLoS Genet 2005; 1: e78.

    Article  Google Scholar 

  7. Carrington M, Nelson GW, Martin MP, Kissner T, Vlahov D, Goedert JJ et al. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 1999; 283: 1748–1752.

    Article  CAS  Google Scholar 

  8. van Manen D, Kootstra NA, Boeser-Nunnink B, Handulle MA, van't Wout AB, Schuitemaker H . Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection. AIDS 2009; 23: 19–28.

    Article  CAS  Google Scholar 

  9. Catano G, Kulkarni H, He W, Marconi VC, Agan BK, Landrum M et al. HIV-1 disease-influencing effects associated with ZNRD1, HCP5 and HLA-C alleles are attributable mainly to either HLA-A10 or HLA-B*57 alleles. PLoS One 2008; 3: e3636.

    Article  Google Scholar 

  10. Houtchens KA, Nichols RJ, Ladner MB, Boal HE, Sollars C, Geraghty DE et al. High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles. Immunogenetics 2007; 59: 525–537.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Koy Saeteurn, Isabel Nocedal, Sherry Hawbecker, Patricia Otto and Samuel Wu for their technical assistance with sample preparation. E Trachtenberg and S Wolinsky conceived and managed the project. M Ladner developed the SNP-based assays and performed all of the SNP genotyping. T Bhattacharya performed all of the statistical analyses. J Phair is the Director of the MACS and oversees all projects using the MACS cohorts. S Wolinsky, H Erlich, T Bhattacharya, M Ladner and E Trachtenberg wrote the paper. All authors have agreed to the content in this paper. This work was supported by grants from the National Institutes of Health (AI 65254-01A1 and AI035039-17).

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Author notes

  1. E Trachtenberg, T Bhattacharya and M Ladner: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Genetics, Children's Hospital Oakland Research Institute, Oakland, CA, USA

    E Trachtenberg, M Ladner & H Erlich

  2. The Santa Fe Institute, Santa Fe, NM, USA

    T Bhattacharya

  3. Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA

    T Bhattacharya

  4. Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    J Phair & S Wolinsky

  5. Department of Human Genetics, Roche Molecular Systems, Pleasanton, CA, USA

    H Erlich

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  1. E Trachtenberg
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  2. T Bhattacharya
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  3. M Ladner
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  4. J Phair
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  5. H Erlich
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  6. S Wolinsky
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Correspondence to E Trachtenberg.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Trachtenberg, E., Bhattacharya, T., Ladner, M. et al. The HLA-B/-C haplotype block contains major determinants for host control of HIV. Genes Immun 10, 673–677 (2009). https://doi.org/10.1038/gene.2009.58

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