Association between the epidermal growth factor rs4444903 G/G genotype and advanced fibrosis at a young age in chronic hepatitis C

Abstract

Background: The epidermal growth factor (EGF) rs4444903 A. G polymorphism has been associated with the development of liver cancer, which commonly complicates cirrhosis of viral origin; however, whether this polymorphism might be associated with fibrosis progression in chronic viral hepatitis is unknown. The present study was performed to assess the allelic and genotypic frequencies of the rs4444903 A. >. G polymorphism in patients with chronic hepatitis C virus HCV infection and to ascertain whether this polymorphism might be an independent predictor of the degree of fibrosis. Methods: An RFLP-PCR technique was used to genotype 645 patients (211 with cirrhosis); 528 were referred for the diagnosis and treatment of chronic hepatitis C, and 117 were transplanted for HCV-related end stage liver disease. A group of 428 healthy subjects served as a control. All the subjects were of Caucasian ethnicity. Results: The EGF rs4444903 A. >. G polymorphism genotype frequencies in HCV chronic infected patients were as follows: A/A = 227 (35.3%), A/G = 328 (50.9%), and G/G =.90 (14.8%). Genotype frequencies were found to differ between patients with an Ishak staging score. ≤. 2 (A/A. =. 117, A/G. =. 157, G/G. =. 34) and patients with a score. >. 2 (A/A. =. 110, A/G. =. 171, G/G. =. 56, p=. 0.038). A highly significant linear relationship between increasing stage scores and EGF genotype was detected in younger patients (A/A: 2.02. ±. 0.18, A/G: 2.55. ±. 0.17, G/G: 3.00. ±. 0.32, p=. 0.008). However, no significant association was detected between the stage score and EGF genotype in older patients (A/A: 3.79. ±. 0.19, A/G: 3.64. ±. 0.15, G/G: 3.98. ±. 0.30 p=. 0.579). Conclusions: The EGF rs4444903 A. >. G polymorphism may facilitate liver fibrosis progression in Caucasian patients with chronic hepatitis C, especially in younger patients. © 2011 Elsevier Ltd.