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


PD Dr. Ralf Lichtinghagen, Department of Clinical Chemistry, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
Tel: +49-511-532-3940.
Fax: +49-511-532-5671.


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)1α(−889), IL1β(−511 and +3954), IL1 receptor agonist (RA)(intron2 VNTR), IL4(intron3 VNTR) and TNFα(−308) loci was performed.

Results: Of the polymorphisms analyzed, IL1β(−511) and IL1RA(intron2 VNTR) were unevenly distributed between the study groups. The IL1β(−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 IL1β(−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.