A set of other variants was also reported GDC-0068 solubility dmso as being associated with response, and in patients of European ancestry they were not statistically distinguishable from rs12979860. The C allele at rs12979860 was positively associated

with SVR. In patients of European ancestry, ≈80% of patients with the C/C genotype cleared the virus, whereas only ≈30% with the T/T genotype did so. The C/C genotype was also more common in European Americans (39%) than African Americans (16%). The difference in allele frequency between these population groups explains approximately half of the difference in response rates between patients of African American versus European ancestry. The association between the rs12979860 SNP and SVR appears to be clinically relevant. Thompson et al.8 reanalyzed the patient population DNA Damage inhibitor from Ge et al.3 on an intent-to-treat basis, meaning that patients were included regardless of adherence. Ethnicity was determined by patient self-reporting. Although including all subjects regardless of adherence does not result in the most powered study design for discovering gene variants influencing therapeutic efficacy, it provides a more accurate picture of the relevance of genotypic information in the clinic, where adherence is variable. Among patients of European ancestry (n = 1,171), SVR was attained by 27% with the T/T genotype, 33% with the C/T genotype, and 69% with the C/C genotype. Among African American patients

(n = 300), SVR was attained by 13% with the T/T genotype, 15% with the C/T genotype, and 48% with the C/C genotype. The presence of only one C allele conferred little benefit in treatment response, as was true in the analyses performed by Ge et al.3 and in the studies of spontaneous clearance reported by Thomas et al.6 African American patients with the C/C genotype had a significantly higher rate of SVR than European Americans who were non-C/C, indicating that genetic background is more important Proteasome inhibitor than ethnicity.

However, response rates were lower for African Americans in each genotype category. In a logistic regression analysis of pretreatmeant (baseline) factors, IL28B status (C/C versus non-C/C) was the strongest predictor of SVR (odds ratio [OR] 5.2; 95% confidence interval [CI] 4.1-6.7). When on-treatment parameters were considered, rapid virological response (RVR, HCV RNA negativity at week 4) was the strongest predictor of SVR, but only a minority of patients (14% of Caucasians) had rapid response. In patients that did have RVR, IL28B remained strongly predictive of SVR, even at 4 weeks after treatment initiation. To identify host genes associated with response to PEG-IFN and RBV, Tanaka et al.4 conducted a genome-wide association study in treatment-adherent Japanese patients with HCV genotype 1 infection. Among the 154 patients, 82 had virological nonresponse (defined as <2 log10 IU/mL reduction in serum HCV RNA at week 12 of treatment), and 72 had a virological response.