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J Med Genet 2005;42:e45 doi:10.1136/jmg.2005.032557
  • Electronic letters

A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C

  1. M M Richardson1,
  2. E E Powell1,2,
  3. H D Barrie1,
  4. A D Clouston1,3,
  5. D M Purdie4,
  6. J R Jonsson1
  1. 1School of Medicine, Southern Clinical Division, The University of Queensland, Brisbane, Australia
  2. 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
  3. 3Concord Repatriation General Hospital, Sydney, Australia
  4. 4Northern California Cancer Center, Fremont, CA, USA
  1. Correspondence to:
 Dr Julie R Jonsson
 University of Queensland, School of Medicine, Southern Division, Level 3, R Wing, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD, 4102, Australia; J.Jonssonuq.edu.au
  • Accepted 25 April 2005
  • Revised 15 April 2005

Abstract

Background: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression.

Methods: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis.

Results: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of ≥3, ≥4, or ≥5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort.

Conclusions: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.

Footnotes

  • Funding for this study was provided by The Perpetual Philanthropic Foundations, The Lions Medical Research Foundation, The Queensland Liver Transplant Trust Fund, The Princess Alexandra Hospital Foundation, The National Health and Medical Research Council, and The Royal Children’s Hospital Foundation.

  • Competing interests: none declared

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