Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin.
OBJECTIVE
In hepatitis C infection, the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect the response to antiviral therapy. Additionally, polymorphisms in the cytokine genes may affect the production of the cytokines. In this study, we determined the frequency of the genotypes associated with polymorphisms of the interleukin-10 and tumor necrosis factor-alpha gene promoters, and transforming growth factor-beta 1 gene leader sequence, and investigated their association with clinical features and the response to interferon-alpha and ribavirin therapy in chronic hepatitis C infection.


METHODS
Genomic DNA from 80 patients and 37 racially matched healthy controls was studied by polymerase chain reaction and direct automated sequencing.


RESULTS
The interleukin-10 -1082 G/G genotype was identified more frequently in patients than in controls (P=0.048). The transforming-growth factor-beta 1 +29 (codon 10) C/C genotype was associated with resistance to the therapy (P=0.029). After adjusting for potential confounding variables, patients exhibiting the C/C genotype were less likely to respond to treatment than patients with the T/T or T/C genotypes.


CONCLUSIONS
These results suggest that inheritance of the interleukin-10 -1082 G/G and the transforming growth factor-beta 1 +29 C/C genotypes, which appear to affect the cytokine production, may be associated with susceptibility to chronic hepatitis C infection and resistance to combined antiviral therapy.
Vidigal
Pedro G
PG
Division of Gastroenterology, Hepatology and Internal Medicine. Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
Germer
Jeffrey J
JJ
Zein
Nizar N
NN
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007372:Interferons / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000998:Antiviral Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D012254:Ribavirin; D007372:Interferons