RVR rates for rs12979860 genotypes in Caucasians were: CC 28% versus selleck chemical CT 5% versus TT 5%; complete EVR rates were CC 87% versus CT 38% versus TT 28%, translating to an overall intent-to-treat SVR rate of 69% in good-response CC patients versus 33% and 27% in CT and TT patients).10 Subsequent studies have shown that this is largely the result of improved phase 1 viral kinetics, with the degree of

viral load reduction clearly different by IL28B genotype as early as 24 h following the first injection of peg-IFN.11,12 Tanaka and colleagues used a two-stage testing approach for their GWAS. They defined their primary response phenotype as virological non-response (VNR; < 2 log reduction in HCV—RNA at 12 weeks) in 80% adherent patients (n = 142). The study used the Affymetrix 6.0 GWAS chip (Santa Clara, CA, USA). The discovery phase identified two significant SNPs that satisfied

criteria after correction for multiple testing (VNR vs SVR, rs12980275 odds ratio [OR]: 26.7, P = 7.41 × 10−13, and rs8099917 OR: 36.5, P = 5.00 × 10−14). XAV 939 These associations were replicated in a second cohort (n = 172); in a combined analysis, the strongest genetic association signal arose from rs8099917 (combined cohorts OR: 27.2, P = 1.11 × 10−27). The large OR in this GWAS likely reflects the relatively extreme phenotype investigated, as shown in the IDEAL dataset: > 97% of Caucasian good-response patients achieve an early virological response,

which inflates the OR. This study did not identify an association between rs12979860 and IFN response. Importantly, this was not a negative result, but reflected the fact that the Affymetrix 6.0 genotyping chip did not include rs12979860 as a tag SNP. Suppiah and colleagues conducted an initial GWAS for SVR in a clinically, well-characterized discovery cohort of patients of European—Australian ancestry (n = 293). Only rs8099917 was found to be genome-wide significant (P = 7.06 × 10−8). A Fossariinae total of 172 SNPs with suggestive association and biological plausability were then assessed in a validation cohort of similar ethnic background (n = 555), confirming the significance of the association between rs8099917 and SVR (combined cohort OR: 1.98, P = 9.25 × 10−9). The strongest association signal in the combined cohort was from another IL28B haplotype SNP (rs12980275, P = 7.74 × 10−10). This GWAS phase used a combination of genotyping platforms (Illumina Infinium Human Hap300 or CNV370-Quad BeadChip; Illumina, USA). Again, data for rs12979860 were not presented. A fourth large European GWAS cohort provided further validation that the IL28B genotype was associated with both treatment-induced and spontaneous viral clearance in a more heterogenous cohort, including patients with prior non-response, non-1 genotypes, and HIV co-infection.