Influence of Host Genes on the Course of Chronic Hepatitis C

Investigators:

Principal Investigators: Timothy Morgan, and Herb Bonkovsky

Don Brambilla; Raymond Chung; Karen Lindsay; David Gretch; Jules Dienstag

NCI Co-Investigators: Michael Dean; Mary Carrington; Tom O'Brien

Hypotheses/Aims

The overall objective of this ancillary study is to evaluate the association between several host genes/alleles and

  1. rate of progression of liver fibrosis and
  2. response to treatment.

Hypotheses

  1. Genetic influences on liver fibrosis.
    1. The following alleles/haplotypes are associated with an increased rate of liver fibrosis:
      • Transforming growth factor-beta 1 (TGF-β1) codon 25 arg/arg
      • Angiotensinogen gene promoter (-6) adenine/adenine
      • Tumor necrosis factor (TNF) promoter alleles -238A and -308A
      • Microsomal epoxide hydrolase exon 3 113 His/His homozygosity
    2. The following HLA alleles are associated with an increased rate of liver fibrosis:
      • B54
      • DQB1*0401
      • DRB1*0405
      • DQB1*0502
    3. Apolipoprotein E-ε4 allele is associated with a decreased rate of liver fibrosis.
    4. The following HLA alleles/haplotypes are associated with a decreased rate of liver fibrosis:
      • alleles: DRB1*1302; DQB1*0604; DRB1*0901; DQB1*0303; DRB1*1101
      • haplotype: DQA1*0201-DQB1*0201
      • haplotype: DRB1*1104-DQA1*0501-DQB1*0301
    5. Heterozygosity at HLA class I and/or class II loci is associated with a decreased rate of liver fibrosis.
  2. Genetic influences on response to treatment with peginterferon plus ribavirin.

    Patients with the following alleles/haplotypes are more likely to be PCR negative after 20 weeks' treatment with peginterferon plus ribavirin:

    • Interleukin-10 promoter alleles -592*A, -819*T or the haplotype ATA ( 1082/-819/-592)
    • HLA haplotype DRB1*1301-DQA1*0103-DQB1*0603