Article Text

Download PDFPDF

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection
Free
  1. M Wright1,
  2. R Goldin1,
  3. S Hellier2,
  4. S Knapp1,
  5. A Frodsham2,
  6. B Hennig2,
  7. A Hill2,
  8. R Apple3,
  9. S Cheng3,
  10. H Thomas1,
  11. M Thursz1
  1. 1Hepatology Section, Division of Medicine A, Imperial College School of Medicine at St Mary’s Hospital, Praed St, London W2 1NY, UK
  2. 2The Wellcome Trust Centre for Human Genetics, University of Oxford, UK
  3. 3Department of Human Genetics, Roche Molecular Systems, Inc, Alameda California 94501, USA
  1. Correspondence to:
    Dr M Wright, Department of Medicine, Imperial College of Science, Technology and Medicine, St Mary’s Hospital (QEQM Wing), South Wharf Rd, London W2 1NY, UK;
    mark.wright{at}ic.ac.uk

Abstract

Background: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects.

Methods: We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation.

Results: The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher’s exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate.

Conclusions: Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.

  • hepatitis C
  • fibrosis
  • rate
  • factor V Leiden
  • polymorphism
  • HCV, hepatitis C virus
  • PCR, polymerase chain reaction
  • ANOVA, analysis of variance
  • ANCOVA, analysis of covariance
View Full Text

Statistics from Altmetric.com

Footnotes

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.