tailieunhanh - báo cáo khoa học: "Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohor"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohor | Smith et al. Genome Medicine 2011 3 57 http content 3 8 57 Genome Medicine RESEARCH Open Access Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort Katherine R Smith1 Vijayaprakash Suppiah2 3 Kate O Connor3 Thomas Berg4 5 Martin Weltman6 Maria Lorena Abate7 Ulrich Spengler8 Margaret Bassendine9 Gail Matthews10 11 William L Irving12 Elizabeth Powell13 14 Stephen Riordan15 Golo Ahlenstiel2 Graeme J Stewart3 Melanie Bahlo1 16 Jacob George2 and David R Booth3 for the International Hepatitis C Genetics Consortium IHCGC Abstract Background The hepatitis C virus HCV infects nearly 3 of the World s population causing severe liver disease in many. Standard of care therapy is currently pegylated interferon alpha and ribavirin PegIFN R which is effective in less than half of those infected with the most common viral genotype. Two IL28B single nucleotide polymorphisms SNPs rs8099917 and rs12979860 predict response to PegIFN R therapy in treatment of HCV infection. These SNPs were identified in genome wide analyses using Illumina genotyping chips. In people of European ancestry there are 6 common more than 1 haplotypes for IL28B one tagged by the rs8099917 minor allele four tagged by rs12979860. Methods We used massively parallel sequencing of the IL28B and IL28A gene regions generated by polymerase chain reaction PCR from pooled DNA samples from 100 responders and 99 non-responders to therapy to identify common variants. Variants that had high odds ratios and were validated were then genotyped in a cohort of 905 responders and non-responders. Their predictive power was assessed alone and in combination with HLA-C. Results Only SNPs in the IL28B linkage disequilibrium block predicted drug response. Eighteen SNPs were identified with evidence for association with drug response and with a high degree of confidence in the sequence