Genome-wide association study and the clinical application to chronic hepatitis C

Abstract

HBased on the data and technology generated in previous international projects, such as the Human Genome Project and the HapMap, for the building of the common patterns of genetic variation in humans, a genome-wide association study (GWAS) to HCV infection was conducted to reveal genetic effects against treatment response or the induction of side effects. Single nucleotide polymorphisms (SNPs) associated with response to pegylated-interferon (PEG-IFN) and ribavirin (RBV) therapy were determined around IL-28B in chromosome 19, and the strong association was also observed in spontaneous viral clearance regardless of population. These data imply that an important interaction between HCV infection and IL-28B is critical for viral persistence or clearance. PEG-IFN and RBV therapy is associated with a range of treatment-limiting adverse effects. One of the frequent side effects induced by the combination therapy is haemolytic anaemia. The severe anaemia requires the reduction of the RBV dose, which could lead to treatment failure. Genetic variants around inosine triphosphatase gene (ITPA) were associated with heamolytic anaemia. Interestingly, the significant SNPs observed in Europe and the United States were not strongly associated with Japanese population although all significant SNPs were located around ITPA gene, suggesting that SNPs typing using individual population are required for the collection of precise data. These significant SNPs would be useful for prediction prior to treatment for individualized medicine.