Cytokine gene polymorphisms and the susceptibility to liver cirrhosis in patients with chronic hepatitis C.
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.
Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
Matthias J
MJ
Bahr
Mohamed
M
el Menuawy
Klaus H W
KH
Boeker
Petra B
PB
Musholt
Michael P
MP
Manns
Ralf
R
Lichtinghagen
D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015375:Receptors, Interleukin-2; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha