IL28Brs12980275 polymorphism shows association with response to treatment in Pakistani patients with Chronic Hepatitis C

Abstract

The aim of this study was to describe the genetic characteristics of Pakistani patients infected with hepatitis C virus (HCV) in relation to IL28B polymorphisms and its association to interferon and ribavirin treatment response. A total of 220 patients, infected with HCV were enrolled, out of which 100 were responders and 120 were nonresponders. The whole blood samples were collected to extract viral RNA and genomic DNA. PCR following the restriction fragment length polymorphism method was used to genotype IL28B rs12979860, rs8099917, and rs12980275 polymorphisms. Liver biopsies and HCV genotyping were performed in nonresponder patients. The rs12980275 AA genotype exhibited significant correlation to treatment response and was found in 62% of the responders and 37.5% of nonresponder patients, whereas AG genotype was noticed frequently in the nonresponder group (P < 0.0001). The rs12979860 CT and rs8099917 TT genotypes were found in 74% and 66% of the responders as compared to 58.3% and 50.8% in nonresponder patients (P = 0.001 and P = 0.032) respectively. HCV 3a genotypes were detected in 50.8% of the nonresponder patients. No significant association was detected between liver biopsy findings and IL28B SNPs (P > 0.05). The results showed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917. This is the first report describing the association of rs12980275 with response to HCV treatment from Pakistan. These findings may help in predicting the outcome of pegylated interferon and ribavirin treatment in HCV patients, and may reduce the side effects and cost of treatment in predicting non-responder patients.

Genetic predictors of the response to the treatment of hepatitis C virus infection

“…The SVR rate was 59.7% in our study group, and it was associated significantly with favorable genotypes of the IL28B gene polymorphisms. Consistent to our findings were the results of the studies of Shaikh et al [25] and Domagalski et al [26]. The study of Shaikh et al included a cohort of 220 Caucasian (Pakistani) patients with chronic hepatitis C treated with PEGIFN/RBV [25].…”

“…Consistent to our findings were the results of the studies of Shaikh et al [25] and Domagalski et al [26]. The study of Shaikh et al included a cohort of 220 Caucasian (Pakistani) patients with chronic hepatitis C treated with PEGIFN/RBV [25]. The SVR rate was 45.5%, and there was a significant association between the SVR and IL28B gene polymorphisms.…”

Prevalence of Hepatitis C Virus Genotypes in Pakistan: Current Scenario and Review of Literature

“…Conclusions drawn by Shaikh et al were in contrast with the analysis in this study, which showed 3a (50.8%) as most prevalent, and exceptionally high frequency of untypable (47%) was observed, followed by 2a (1.6%). All other genotypes were not seen in a total of 120 sample size (68).…”

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study

“…While the Urdu speaking ethnic community has heterogeneous Indian ancestry [56]. Thus the genetic variations exhibit significant differences in the risk of developing various disorders and disease progression in the Pakistani population [15,57,58].. Majority of the preeclamptic patients in our study were Sindhi (56%) and Urdu (27.2%) speaking.…”

“…The common SNVs found in association with preeclampsia include F5: c.1601G > A (rs6025), MTHFR: c.665C > T (rs1801133), MTHFR: c.1286A > C (rs1801131), VEGFA: c.-2055A > C (rs699947) and VEGFA: c.*237C > T (rs3025039) [12][13][14]. The influence of the SNVs on disease outcome is variable among different world populations, possibly due to ethnic variations and the findings may not be generalized [15].…”