Programmed Cell Death-1 Polymorphism rs11568821 is a predictor of Treatment Outcome in Chronic HCV Genotype 4 Infection

Abstract

Background & Aim: Recently, a single nucleotide polymorphism of Programmed Cell Death-1 (PD-1) gene has been reported to be associated with sustained virologic response (SVR) and to increase the predictive value of IL28B/CC genotype in chronic hepatitis C virus (HCV) genotype 1 and 3 infections. However, to date, there is no data concerning genotype 4. The aim of this study was to investigate the effect of PD-1.3 polymorphism on treatment outcome in patients with chronic HCV-4 infection. Methods: 200 HCV-4 chronic infected patients were recruited and received PEG- IFN-α and ribavirin therapy. They were classified according to their response to treatment into SVR and Non-responders (NR) groups. PD-1.3 and IL28B rs12979860 polymorphisms were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis. Results: PD-1.3/GG genotype was over-represented in NR (79.8%) than in SVR patients (58.3%), P=0.001. PD-1.3/A allele was associated with SVR (P <0.001). IL28B/CC genotype was recognized in 60.4% of SVR vs. 25.9% of NR patients (P <0.001). The unfavorable TT genotype was revealed in 4.2% of SVR vs. 23.1% of NRs (P<0.001). Using logistic regression analysis, IL28B/CC genotype showed a predictive value of 58% which increased to 62.8% in the presence of PD1.3/AA genotype. Conclusions: PD-1.3 polymorphism is a new predictor of treatment outcome in chronic HCV genotype 4 infected patients and allele a associates with SVR. Genotyping of both IL28B rs12979860 and PD-1.3 is valuable in these patients for early prediction of the response to combined interferon and ribavirin therapy.