Relation of HCV induced insulin resitance and Hepatocellular carcinoma: Role of MDR1 gene C.335t>C and C.3073A>C SNPS

Abstract

Hepatocellular carcinoma (HCC), is the most common primary liver tumor. HCV-associated insulin resistance (IR) may cause hepatic steatosis, hepatic fibrosis and hepatocarcinogenesis. The multidrug resistance 1 gene (MDR1) is a candidate gene for susceptibility to HCC.. The aim of the current study was to evaluate the association of the MDR 1 gene c.335T>C and the c.3073A>C SNPs with HCV induced HCC and to correlate this to
insulin resistance state. A total of 205 HCC patients (on top of HCV) were enrolled in this study. Genotyping of MDR1 gene SNPs was done by PCR-RFLP.Results revealed that the association of genotypes/alleles from the c.335T.C and c.3073A.C SNPs with the risk of HCC. There was a significantly increased risk of HCC in chronic HCV that was associated with hepatic steatosis. The CC genotype of the c.335T>C polymorphism was associated with an increased risk of developing HCC compared to the
TT genotype.It could be concluded from this work that HCV-related metabolic complications as hepatic steatosis and IR may be associated
with increased risk of HCC development. c.335T>C and c.3073A>C SNPs of MDR1 gene could be considered as a possible molecular candidates for the HCC development in chronic HCV patients.

Key words: HCV-HCC-Insulin Resistance -steatosis-MDR1gene
polymorphism