Cytokine gene polymorphisms and the susceptibility to liver cirrhosis in patients with chronic hepatitis C

Liver Int. 2003 Dec;23(6):420-5. doi: 10.1111/j.1478-3231.2003.00873.x.

Abstract

Background: The speed of fibrosis progression varies considerably between patients with chronic hepatitis C. This study analyzed whether cytokine gene polymorphisms are associated with a progressive course of the disease.

Methods: Leukocyte DNA from 101 patients with chronic hepatitis C, 52 patients with hepatitis C virus (HCV)-induced cirrhosis and 200 Caucasian blood donors was prepared. Using PCR, RFLP and PAGE, gene polymorphism analysis of the interleukin (IL)1alpha( - 889), IL1beta( - 511 and +3954), IL1 receptor agonist (RA)(intron2 VNTR), IL4(intron3 VNTR) and TNFalpha( - 308) loci was performed.

Results: Of the polymorphisms analyzed, IL1beta( - 511) and IL1RA(intron2 VNTR) were unevenly distributed between the study groups. The IL1 (- 511)*A2A2 genotype occurred significantly more often in chronic hepatitis C and HCV-induced liver cirrhosis than in the controls (P < 0.01, P < 0.05, respectively). Patients with HCV-induced cirrhosis displayed a significantly higher frequency of the IL1RA(intron2 VNTR)*A2 polymorphism than patients with chronic hepatitis C and controls (P < 0.05).

Conclusions: Although the IL1beta( - 511)*A2A2 genotype may increase the susceptibility to acquire chronic hepatitis C and IL1RA(intron2 VNTR)*A2 polymorphism is associated with disease progression to cirrhosis, our results indicate that the analyzed cytokine gene polymorphisms have an overall low impact on the natural course of chronic hepatitis C infection.

MeSH terms

  • Cytokines / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Interleukin-2 / antagonists & inhibitors
  • Sialoglycoproteins / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Interleukin-2
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha