CTLA-4 Gene Haplotypes and the Risk of Chronic Hepatitis C Infection; a Case Control Study

The prevalence of hepatitis C virus (HCV) infection is increasing worldwide. Cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) may play a role in the intensity of the disease. The aim of this study was to evaluate the association between genetic variants of the CTLA-4 and HCV infection.Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was performed as the genotyping assay at four different positions (+49 A>G, -318 C>T, -1722 T>C, and - 1661 A>G). Haplotypes were analyzed using PHASE software. Sixty-five HCV patients and 65 healthy individuals as controls who were referred to the hepatitis clinic in Mashhad, Iran, were recruited. Genomic DNA was extracted from whole blood of participants.In a dominant analysis model of the -1661 position (GG vs. AA+AG), the AA genotype was more common in controls than in patients (adjusted P = 0.0003; OR = 0.15, 95% CI = 0.051 -0.42). The GCAT haplotype was also more prevalent in controls than in patients (adjusted P = 0.01; OR = 0.40, 95% CI = 0.20-0.81). Furthermore, the ACGT/ACGT diplotype was more common in controls than in patients (P = 0.0037; OR = 0.15, 95% CI = 0.04-0.54). In addition, the ACGT/ACAT diplotype was more frequent in patients than controls (adjusted P =0.003; OR = 2.48, 95% CI = 1.37- 4.50).Our results indicated that polymorphisms in CTLA-4 and certain haplotypes may affect the risk of HCV infection in our population, although a larger sample size may be required to confirm this association.