Ge et al. and Suppiah et al. studied genetic variants associated with SVR to PEG-IFN/RBV therapy in individuals infected with HCV genotype 1.17,18 McHutchison et al. found genetic factors using patients from the IDEAL trial,21 a large randomized controlled trial involving Caucasian, American-African, and Hispanic individuals
in North America (n = 1137) (Table 1). The latter study group analyzed Caucasians consisting of 293 Australians of Northern European learn more ancestry with HCV genotype 1, and also validated the results in an independent replication cohort consisting of 555 Europeans from the UK, Germany, Italy and Australia. These two study groups mainly investigated GWAS in Caucasians, and analyze host factors associated with SVR. Tanaka et al. examined 142 Japanese patients with chronic hepatitis C infected with HCV genotype 1 for GWAS, and prepared an independent replication cohort of 172 Japanese (Table 1).20 Especially, Tanaka et al. divided patients into three groups, SVR, TVR, or NVR, and NVR versus virological responder (VR) consisting of SVR and TVR was also used for the predication of NVR factors (Fig. 1). Rauch et al. investigated
465 Caucasians infected with HCV genotypes 1, 2, 3 or 4 to reveal genetic variations associated with response to the combination therapy.19 A case-control study was designed to detect genetic variations related selleckchem to SVR in European individuals. Three study groups except Suppiah et al. selected patients receiving at least 80% of the recommended treatment dose to emphasize genetic associations. Ge et al. identified a genetic see more polymorphism (rs12979860)
near the IL-28B gene on chromosome 19, encoding IFN-λ3 (IFN-λ3). Individuals with the CC genotype showed the association with an approximately twofold better response to PEG-IFN/RBV treatment compared with those with the TT genotype, both among patients of European ancestry (P = 1.06 × 10−25) and African-Americans (P = 2.06 × 10−3). Both Suppiah et al. and Tanaka et al. revealed the most significant SNPs, rs8099917 (8 kb upstream of IL-28B) associated with SVR in patients of European and Japanese. Suppiah et al. also identified the association of rs8099917 in European ancestry with HCV genotype 1 based on the determination of SVR factors (combined P = 9.25 × 10−9, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.57–2.52) (Table 1).17 The population with risk allele rs8099917 showed low levels of IL-28A/B mRNA by real-time polymerase chain reaction (PCR).17,20 Rauch et al. involved patients infected with HCV genotypes 1, 2, 3, or 4. They also identified several SNPs around the IL-28B gene on chromosome 19.19 The strongest association with treatment failure was found with rs8099917 (P = 5.47 × 10−8; OR = 5.19). Interestingly, rs8099917 did not associate with the response to PEG-IFN&RBV therapy in genotype 2 or 3 patients.