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WITHDRAWN: Analysis of host genetic variations associated with response to anti-HCV therapies in global populations

M. Irfan,Sarah Rizwan Qazi,M. Shakeel,Saeed Khan,Zahid Azam,M. Shahzad,I. Khan

Published 2021 in Meta Gene

ABSTRACT

Abstract Hepatitis C virus (HCV) is a global health issue infecting 71 million people chronically. Host genetic variants have significant role in the prediction of better treatment response as well as the modulation of the side effects of anti-HCV therapies. Assessment of frequencies of such genetic variants in global populations has not been performed so far. In current study, we highlight the allele/genotype frequency pattern of SNPs associated with the prediction of sustained virologic response (SVR) to antiviral therapies such as sofosbuvir, daclatasvir, pegylated (PEG)-IFN and ribavirin (RBV) across the global populations. We compiled a list of genes (n = 203) involved in the host immunity, inflammatory response, surface receptor for virus attachment and pharmacogenes by using deep literature survey and manually curated databases such as Pharmacogenomics Knowledge Base (PharmGKB), and PharmacoGenomic Mutation Database (PGMD). We identified 200 SNPs in 66 genes associated with the treatment response with different combinations of PEG-IFN/RBV, sofosbuvir and daclatasvir antiviral therapies reported in different continental populations. Several variants such as rs12979860, rs368234815, rs12980275, rs4273729 significantly involved in the prediction of better treatment response to direct acting viral agents and PEG-IFN/RBV. The genotype frequency of variants such as rs12979860 “CC”, rs368234815 “TT”, rs4803217 “CC”, and s12980275 “AA” was found high (up to 84%) in Asian populations followed by European (~60%) and American populations (~50%) whereas low in African populations (~20%) by using the whole genome sequence data of 1000 genomes project. Genetic differentiation analysis using the prioritized variants illustrated that African populations are well differentiated with other continental populations. Hence, this study compiles a comprehensive landscape of variants associated with HCV treatment, and may be useful in clinical decision to explore suitability of current and future therapies in different populations.

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