Combining the determinants of the IFN-λ3 rs12979860 and rs8099917 gene variants has recently been shown to improve the predictive response to dual therapy with PEG-IFN plus RBV in
Proteasome inhibitor chronic HCV Gt1 infection.[19] In particular, heterozygote carriers of the rs12979860 non-responder T allele (i.e. IFN-λ3 CT genotype), in contrast with homozygotes for the rs12979860 responder C allele, may derive benefit by additional genotyping of the rs8099917 SNP in relation to response prediction. The SVR in IFN-λ3 CT subjects is 55% in the presence of the responder rs8099917 TT genotype compared with only 40% in those who carry the rs8099917 TG or GG genotype.[19] In our study, we found that one-third of Caucasians (18% of cohort) and over half of the Aboriginals (29% of cohort) with IFN-λ3 CT genotype carried the rs8099917 TT genotype and thus had an increased chance of SVR. Although this genetic epidemiological study has several strengths, including its size, coverage of both IFN-λ3 SNPs, as well as a diverse range of ethnic groups, it also has its limitations. In particular,
RG7204 research buy it focuses only on chronic HCV Gt1 subjects under consideration for or receiving treatment with PEG-IFN plus RBV. Thus, the distribution of IFN-λ3 genotypes among HCV Gt1 subjects may not be applicable to non-Gt1 HCV subjects as suggested by recent data from both Europe and Asia.[13, 20] Second, the numbers of subjects in certain ethnic groups was relatively small (e.g. Maoris), and thus, caution is needed when extrapolating these results to the wider population from these ethnic backgrounds. Furthermore, the overall study population was recruited from two separate studies, including a prospective observational study and CHARIOT, a prospective interventional study of high-dose PEG-IFN. Still, learn more the two cohorts had relatively similar baseline characteristics
and were generally representative of the Australian population with chronic HCV. There was however a small but appreciable increase in the number of Asians in CHARIOT. This likely explains why the overall frequency of favorable IFN-λ3 genotypes was higher in this cohort. Finally, the study does not address either the impact of IFN-λ3 testing on treatment uptake or the relationship between IFN-λ3 status and treatment response among the different ethnic populations. In conclusion, this study is the largest yet to report the distribution of IFN-λ3 polymorphisms in treatment-naïve HCV Gt1-infected subjects. The results show the distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 HCV in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maoris/Pacific Islanders than Caucasians and Aboriginals.
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