There is an urgent need of personalized GSK2656157? therapy for chronic hepatitis C. The fact that about 30% of patients achieve natural clearance following acute hepatitis C virus infection and ethnic differences in response to treatment suggests that host genetic variation plays a critical role in the drug response[2,11,17,19,20]. Four recent studies have found that two SNPs, rs8099917 and rs12979860, located near the IL28B gene were highly associated with treatment response and spontaneous clearance following acute hepatitis C infection[15,17-19]. Subsequent studies found that the two SNPs had an impact on the occurrence of various side effects of the combined therapy, treatment response and the HCV RNA genotype distribution of the infecting virus[23,24].
Other studies have shown that IL28B polymorphisms were a significant, independent predictive factor regardless of HCV genotype or HCV RNA load. The determination of IL28B polymorphisms may assist in evaluating the likelihood of response to treatment with peg-interferon and ribavirin therapy in patients chronically infected with HCV, especially for genotype 1 patients[25-28]. The recent significant findings regarding IL28b SNPs and the genotyping of HCV showed how personalizing treatment for HCV infection may be possible[24-27]. The development of an accurate assay for the detection of rs8099917 and rs12979860 polymorphisms, and progress in HCV genotyping will help both clinicians and patients choose the treatment regimen and its anticipated duration[22] and this may be an early step in the era of personalized therapy for chronic hepatitis C[20,29,30].
Host genetic diversity is of great significance in making an informed decision regarding the risk-benefit treatment and the likelihood of success for any individual treatment, so developing a simple, rapid and clinically available assay is an urgent demand. An assay that could accurately and rapidly detect the IL28b SNPs is a priority for clinical practitioners. Developing a novel and efficient assay for the detection of IL28B polymorphisms has been the focus of numerous researches. Direct sequencing of PCR amplicons, restriction fragment length polymorphism (RFLP) and traditional microarrays are valuable research techniques. However, the technical demands of these assays make them unsuitable for routine diagnostic use in clinical practice.
For example, direct sequencing is technologically complicated, time-consuming and needs special expertise[28,29]. The RFLP is almost impossible to be used for the detection of all significant SNPs since it requires a specific cutting site and restriction enzyme for the particular site[31]. Microarray assays widely used in the previous research, GSK-3 apart from being provided by specialized and high-cost facilities, can only detect either of the two SNPs separately[19,21-23]. No microarray assay was available currently that can detect the two SNPs simultaneously.