Pharmacogenomics of chronic hepatitis C therapy with genome-wide association studies

摘要

Chronic hepatitis C (CHC) is a liver disease characterized by infection with the hepatitis C virus (HCV) persisting for more than six months. Patients with CHC often stop pursuing the pegylated interferon (peg-IFN) and ribavirin (RBV) treatment because of the high cost and associated adverse effects. Therefore, it is highly desirable, both clinically and economically, to establish the determinants of response to distinguish responders from nonresponders, and to predict the possible outcomes of the peg-IFN and RBV treatments. The aim of this study was to review recent data on the pharmacogenomics of the drug efficacy of IFN in CHC patients. Single nucleotide polymorphisms (SNPs) can be used to understand the relationship between genetic inheritance and IFN therapeutic response. In the recent advent of scientific research, the genome-wide association study (GWAS), which is an alternative to the candidate-gene approach, is widely utilized to examine hundreds of thousands of SNPs by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been employed to study the determinants of HCV’s response to therapy. Several recent findings have demonstrated that some SNPs in the interleukin 28B gene are closely associated with IFN responsiveness. These results promise to lead to mechanistic findings related to IFN responsiveness in this disease, and will probably have major contributions for individualized medicine and therapeutic decision making.