Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

Authors

  • Leland J. Yee,

    1. Program in Epidemiology of Infection and Immunity, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
    2. Division of Gastroenterology and Hepatology (UAB Liver Center), University of Alabama at Birmingham, Birmingham, Alabama
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  • Jianming Tang,

    1. Program in Epidemiology of Infection and Immunity, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
    2. Division of Geographic Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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  • Andrew W. Gibson,

    1. Division of Clinical Immunology and Rheumatology (UAB Arthritis Center); Department of Medicine, School of Medicine; University of Alabama at Birmingham, Birmingham, Alabama
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  • Robert Kimberly,

    1. Division of Clinical Immunology and Rheumatology (UAB Arthritis Center); Department of Medicine, School of Medicine; University of Alabama at Birmingham, Birmingham, Alabama
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  • Dirk J. van Leeuwen,

    1. Division of Gastroenterology and Hepatology (UAB Liver Center), University of Alabama at Birmingham, Birmingham, Alabama
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  • Richard A. Kaslow M.D., M.P.H.

    Corresponding author
    1. Program in Epidemiology of Infection and Immunity, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama
    2. Division of Geographic Medicine, University of Alabama at Birmingham, Birmingham, Alabama
    • 220A Ryals Public Health Building, University of Alabama, Birmingham, 1665 University Boulevard, Birmingham, AL 35294-0022. fax: 205-934-8665.
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Abstract

Host genetic factors have been reported to influence the natural history of hepatitis C virus (HCV) infection. We examined whether variation in interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) genes would predict the likelihood of sustained response to antiviral therapy. Single nucleotide polymorphisms (SNPs) and microsatellites at two loci encoding the cytokines IL-10 and TNF-α were determined by polymerase chain reaction (PCR)-based techniques. Their relationship to the outcome of antiviral therapy for chronic HCV infection was studied in 49 white patients who had a virologically sustained response (SR) and in 55 white nonresponders (NR) to a combination of interferon alfa-2b and ribavirin (IFN + R). Several IL-10 variants were more frequent among SRs compared with NRs. Carriage of the −592A or the −819T SNP was associated with SR (odds ratio [OR] = 2.2; P = .016). The −592A/A and the exclusively linked −819T/T genotypes were also associated with SR (OR = 16.6; P = .013 for either). The haplotype consisting of the 108-bp IL-10.R microsatellite and −3575T, −2763C, −1082A, −819T, −592A was also associated with SR (OR = 2.65; P = .01). Stratification for viral genotype, baseline viral RNA concentration, and histologic status identified homozygosity for the haplotype as the principal determinant: all 5 homozygous individuals achieved SR (ORcrude = 13.7; P = .025; stratified ORs = 1.9-7.0), whereas heterozygotes differed only slightly from wild-type carriers. In contrast, TNF alleles defined by promoter sequences −238G/A and −308G/A were approximately equally distributed among SR and NR. In conclusion, homozygosity for −592A, −819T or the extended haplotype (108bp) − (−2575T) − (−2763C) − (−1082A) − (−819T) − (−592A) is associated with SR to IFN + R.

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