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Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Genes & Immunity volume 9, pages 328–333 (2008)Cite this article

Abstract

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30–80%) and lower response rates have been reported among African Americans (AA; ∼30%) compared to Caucasian Americans (CA; ∼50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-α-2a and ribavirin. We observed carriage of A*02 (RR=1.33(1.08–1.64); P=0.008), B*58 (RR=1.84(1.24-2.73); P=0.002) and DPB1*1701 (RR=1.57(1.09-2.26); P=0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

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Acknowledgements

This clinical study was a cooperative agreement funded by the NIDDK and co-funded by the National Center on Minority Health and Health Disparities (NCMHD), with a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. Grant numbers: U01 DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349 and U01 DK60341. Other support: National Center for Research Resources (NCRR), NIDDK Intramural Program (TJL), National Cancer Institute, Center for Cancer Research, General Clinical Research Centers Program Grants: M01 RR00645 (New York Presbyterian), M02 RR000079 (University of California, San Francisco), M01 RR16500 (University of Maryland), M01 RR000042 (University of Michigan) and M01 RR00046 (University of North Carolina). Additional support for Dr Leland J Yee was provided by a National Institutes of Health Clinical Research Career Development Award Grant 1KL2 RR024154-02.

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Authors and Affiliations

  1. Cedars Sinai Medical Center, Los Angeles, CA, USA

    S L Rhodes, X Tong, X Su & H Yang

  2. Roche Molecular Systems, Inc., Alameda, CA, USA

    H Erlich, J Wang, J Li & T Bugawan

  3. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    K A Im

  4. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    K A Im & L J Yee

  5. Department of Medicine, Center for Liver Diseases, Veterans Affairs Medical Center, Miami, FL, USA

    L Jeffers

  6. Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver, CO, USA

    H R Rosen

  7. Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    L J Yee

  8. Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD, USA

    T J Liang

  9. Department of Discovery, Medicine and Epidemiology, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA

    H Yang

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for the Virahep-C Study Group

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Correspondence to L J Yee.

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

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Rhodes, S., Erlich, H., Im, K. et al. Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection. Genes Immun 9, 328–333 (2008). https://doi.org/10.1038/gene.2008.21

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