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

• DOI: 10.1186/gm273
• Publication Date: 2011-09-01T18:28:55Z
• Authors: Katherine R Smith; Vijayaprakash Sup...; Kate O'Connor; Thomas Berg; Martin Weltman; Maria Lorena Abate; Ulrich Spengler; Margaret Bassendine; Gail Matthews; William L Irving; Elizabeth Powell; Stephen Riordan; Golo Ahlenstiel; Graeme J Stewart; Melanie Bahlo; Jacob George; David R Booth
• Keywords: Minor allele frequency; Linkage Disequilibrium

The hepatitis C virus (HCV) infects nearly 3% of the World's population, causing severe liver disease in many. Standard care therapy is currently pegylated interferon alpha and ribavirin (PegIFN/R), which effective less than half those infected with most common viral genotype. Two IL28B single nucleotide polymorphisms (SNPs), rs8099917 rs12979860, predict response to (PegIFN/R) treatment HCV infection. These SNPs were identified genome wide analyses using Illumina genotyping chips. In people European ancestry, there are 6 (more 1%) haplotypes for IL28B, one tagged by minor allele, four rs12979860. We used massively parallel sequencing IL28A gene regions generated polymerase chain reaction (PCR) from pooled DNA samples 100 responders 99 non-responders therapy, identify variants. Variants that had high odds ratios validated then genotyped a cohort 905 non-responders. Their predictive power was assessed, alone combination HLA-C. Only linkage disequilibrium block predicted drug response. Eighteen evidence association response, degree confidence sequence call. found two SNPs, rs4803221 (homozygote allele positive value (PPV) 77%) rs7248668 (PPV 78%), failure respond better current best, 73%) rs12979860 68%) this cross-sectional cohort. best haplotype, haplotype 2. Genotypes lack alleles. However, 2 carrier status HLA-C C2C2 genotype, has previously been reported improve prediction provides highest PPV (80%). present alternative putative transcription factor binding methylation sites. Massively allowed identification comparison identifying HCV. tagging have PPV, especially functional basis may be due altered regulation gene. approaches utility improving diagnostic testing causal or SNPs.