Genetic polymorphisms of inflammatory cytokines and liver fibrosis progression due to recurrent hepatitis C.
To ascertain whether single nucleotide polymorphisms (SNPs) regulating the expression of interferon-gamma (IFN-gamma), IFN-gamma receptor-1 (IFNGR-1), interleukin-6 (IL-6), IL-10, IL-18, and tumor necrosis factor-alpha (TNF-alpha) may be associated with early fibrosis progression of recurrent hepatitis C, 50 liver transplantation recipients (32 men, 18 women, median age 56 years) with a median histologic follow-up time of 54 months were studied; 98 healthy blood donors served as controls. Cytokine SNPs were determined by means of previously described PCR-based methods. On the basis of the SNP studies, a low, intermediate, or high producer cytokine phenotype was attributed to each patient. Only 1 of the 17 low IL-10 producers reached an Ishak staging score > 2, in contrast to 20 of the 33 patients who were intermediate or high IL-10 producers (Mantel-Cox, p < 0.005). Recipients who were low IL-10 producers and high IFN-gamma producers had significantly slower fibrosis progression in comparison to intermediate/high IL-10 producers and low IFN-gamma producers (p < 0.005). In conclusion, cytokine SNPs resulting in high and low producer phenotypes of both Th1 and Th2 cytokines appear to modulate the course of recurrent hepatitis C. Low IL-10 producers are those with the slowest histologic fibrosis progression.
Falleti
Edmondo
E
Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Italy.
Fabris
Carlo
C
Toniutto
Pierluigi
P
Fontanini
Elisabetta
E
Cussigh
Annarosa
A
Caldato
Maja
M
Rossi
Elisabetta
E
Bitetto
Davide
D
Minisini
Rosalba
R
Smirne
Carlo
C
Pirisi
Mario
M
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000601:surgery; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D018836:Inflammation Mediators