Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection.
Immune response to viral infection is an important determinant of liver injury in chronic hepatitis C (CHC). Experimental and clinical data suggest a protective role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4) was investigated on (i) susceptibility to CHC, (ii) progression of hepatic fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1 infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage 1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3 in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found between the SNP4 allele and the presence of cirrhosis (P=0.01). Homozygous SNP4 individual variants segregated within the cirrhosis group (P=0.03). We found neither an association with SNP3 nor with the necroinflammatory disease activity (as measured by ALT levels) nor with the response to antiviral therapy. Our work implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic cirrhosis in HCV genotype-1 infection.
Hofer
H
H
Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
Neufeld
J B
JB
Oesterreicher
C
C
Grundtner
P
P
Wrba
F
F
Gangl
A
A
Ferenci
P
P
Gasche
C
C
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D053701:Receptors, Interleukin-10; D012254:Ribavirin / Q000494:pharmacology
D000998:Antiviral Agents; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D012254:Ribavirin; D007372:Interferons