Multivariate binary logistic regression analysis was used to identify the association of the rs12979860, rs8099917, rs12980175, and rs8103142 variations and haplotypes with SVR. In doing so, adjustments were performed regarding age, sex, HCV RNA levels, and fibrosis stage. Data were phased using fastPHASE.35 Structure

of LD was analyzed with Haploview 4.2 (Broad Institute, Cambridge, MA). We aimed to estimate both recessive and additive effects of the SNPs. In the study cohort of 942 patients, the overall genotype distribution of Selleckchem Rapamycin IL28B rs12979860 CC, CT, and TT was 34%, 52%, and 14%, and the distribution of rs8099917 TT, TG, and GG was 56%, 40%, and 5%, respectively. Distribution of rs12980275 and rs8103142 is depicted in Table 2. The responder genotypes, rs12980275AA and rs8103142TT, showed frequencies of 36% and Selleck Nutlin-3a 31%, respectively. The allelic frequencies were almost the same for rs12979860, rs12980275, and rs8103142. Significant deviations

from Hardy-Weinberg’s equilibrium in genotype distribution were observed for the SNPs as follows: rs12979860: P = 0.012; rs8099917: P = 0.022; and rs12980275: P = 0.012. The combined assessment of all SNPs showed frequencies for the most prevalent genotypes, rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TT, rs12979860CT/rs8099917TG, rs12979860CC/rs8099917TT/rs12980275AA, and rs12979860CT/rs8099917TG/rs12980275AG, of 31%, 22%, 30%, 30%, and 29%, respectively (Supporting Table 3A). The remaining genotypes for the combined SNPs were less frequent, and, in particular, some variants showed rare frequencies of 0.2%-0.5%. The confirmation cohort showed similar genotype frequencies (Table 2; Supporting Table 3B). At first, we performed single SNP and genotype analysis of data. Within the cohort of 942 patients, 495 (54%) had SVR. SVR rates were 68%, 46%, and 41% for rs12979860 CC, CT, and TT and 62%, 42%, and 35% for rs8099917 TT, TG, and GG, respectively. Both SNPs, rs129780275 and rs8103142,

showed similar SVR rates (Supporting Table 4). In univariate analyses (shown in Fig. 1), the CC homozygous genotype of rs12979860 reached a high level of association with SVR (CC versus CT: P = 2.6 × 10−7; CC versus TT: P = 2.1 × 10−7). The TT major homozygous genotype of rs8099917 was significantly associated with SVR (TT versus TG: P = 1.1 × 10−8; TT versus medchemexpress GG: P = 0.001). The homozygous rs12980275AA and rs8103142TT variants were also significantly correlated with SVR (AA versus AG: P = 6.1 × 10−6; AA versus GG: P = 2.2 × 10−6; TT versus CT: P = 0.031; TT versus CC: P = 0.001). The heterozygous genotypes of rs12979860, rs8099917, rs12980275, and rs8103412 displayed a nonresponder allelic pattern (P > 0.05). Adjusting for the covariates of age, sex, HCV RNA level, and the stage of histological fibrosis, a multivariate logistic regression model was performed (Fig. 2). In the first regression model, all covariates were included, except for rs8099917.