Association between SNPs of Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1)and the susceptibility to chronic Hepatitis C infection in virus C-infected patients

Abstract

BackgroundCytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are immune inhibitory factors that provide inhibitory signals to T cells. MethodsA case-controlled genetic association study was conducted in478 patients (160 patients with chronic Hepatitis C virus (HCV) and diabetes mellitus (DM) and156 patients with chronic HCV without DM) and162healthy controls. We genotyped selected single nucleotide polymorphisms (SNPs) of rs10204525 and rs231775using real-time-polymerase chain reaction (RT-PCR). ResultsOur study revealed thatthers10204525 CT genotype was significantly associated with a high susceptibility to chronic HCV infection and to HCV+DM (adjusted odds ratio (OR)7.531, 95% confidence interval (CI):4.099–13.836, P < 0.0001 and adjusted OR 7.791, 95% CI:4.244–14.303, P < 0.0001, respectively).In addition, the frequency of CT+TT genotypes versus the CC genotype and the T allele versus the C allele were elevated in non-responder patients to antiviral therapy compared with responder patients (P < 0.0001) in HCV group. For rs231775,the AG genotype was significantly associated with a high susceptibility to chronic HCV infection and HCV infection with DM (adjusted OR 5.124,95% CI:3.150–8.334, P < 0.0001 and adjusted OR 20.594, 95% CI:11.026–38.467, P < 0.0001, respectively).Furthermore, the frequency of AG+GG genotypes versus the CC genotype and the G allele versus the A allele was elevated in non-responder patients to antiviral therapy when compared with responder patients in the HCV and HCV+DM groups(P < 0.05). ConclusionsBoth rs10204525 and rs231775 are associated with a risk of chronic HCV, with or without DM.