9, 10 Functional ITPase prevents the incorporation of undesired purine base analogs into nucleic acids; this hydrolyzes them into monophosphates,

so their deleterious effects are avoided. Although the exact mechanisms of RBV-induced hemolytic anemia are still not fully understood, PS341 these SNPs have already been identified as responsible for thiopurine analog toxicity and adverse sensitivity to purine base analog drugs.9, 11 Thus, the identified SNPs are excellent examples of important metabolic pathways that determine the effects and toxicities of different drugs. What might be the clinical consequences of these findings? We are certainly living in a very exciting time in which new disease-associated polymorphisms are being identified almost every day and are being published in the most prestigious

journals.12 These expensive and labor-extensive investigations are mainly performed for two reasons. The first aim is better risk prediction of a clinical phenotype in affected or treated patients; the second aim is the identification of key molecular pathways in the pathogenesis of the disease under investigation that might later lead to novel therapeutic options. In chronic HCV infection, the first aim has been put forward a lot in past years. In the near future, the following Paclitaxel mw scenario seems imaginable: in a given individual with chronic HCV infection and low baseline fibrosis,

we could genotype for the cirrhosis risk score and determine the likelihood of severe fibrosis developing. If this is the case, we will have a clear indication for antiviral therapy. As long as this is based on pegylated interferon and RBV, we will genotype for IL28B variants and determine medchemexpress the likelihood of a positive response to therapy. When IL28B wild-type alleles are found, there is a high chance of successful therapy, and we will continue genotyping for ITPA gene variants to determine the risk for RBV-induced hemolytic anemia. We can also test for gene polymorphisms that are associated with interferon-induced expression,13 and further variants for treatment side effects will certainly be identified. However, although this scenario might be advantageous for patients who are carriers of the low-risk alleles, the question of what happens with subjects with at-risk alleles of the SNPs arises. Would we really exclude patients with IL28B or ITPA risk variants from antiviral therapies? The answer is probably no. Therefore, the second aim of genome-wide association studies needs to be pushed further. Only when we have translated the genetic findings into new tailored therapies based on functional studies of the identified gene pathways will the era of personalized medicine in hepatitis C have been reached.