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

Richardson, M. M., Powell, E. E., Barrie, H. D., Clouston, A. D., Purdie, D. M. and Jonsson, J. R. (2005) A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C. Journal of Medical Genetics, 42 7: 1-6.


Author Richardson, M. M.
Powell, E. E.
Barrie, H. D.
Clouston, A. D.
Purdie, D. M.
Jonsson, J. R.
Title A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C
Journal name Journal of Medical Genetics   Check publisher's open access policy
ISSN 0022-2593
Publication date 2005
Sub-type Article (original research)
DOI 10.1136/jmg.2005.032557
Volume 42
Issue 7
Start page 1
End page 6
Total pages 6
Editor C. Eng
Place of publication London
Publisher B M J Publishing Group
Collection year 2005
Language eng
Subject C1
321010 Infectious Diseases
730101 Infectious diseases
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.
Keyword Genetics & Heredity
Triglyceride Transfer Protein
Density-lipoprotein Receptor
Alcoholic Liver-disease
Virus-infection
Superoxide-dismutase
Oxidative Stress
Natural-history
Fibrosis
Chemokine
Susceptibility
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2006 Higher Education Research Data Collection
School of Medicine Publications
 
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