CTLA-۴ Gene Haplotypes and the Risk of Chronic Hepatitis C Infection; a Case Control Study

Background: The prevalence of hepatitis C virus (HCV) infection is increasing worldwide. Cytotoxic T-lymphocyte-associated protein ۴ (CTLA-۴) 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-۴ and HCV infection. Methods: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was performed as the genotyping assay at four different positions (+۴۹ A>G, -۳۱۸ C>T, -۱۷۲۲ T>C, and -۱۶۶۱ A>G). Haplotypes were analyzed using PHASE software. Sixty-five HCV patients and ۶۵ 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. Results: In a dominant analysis model of the -۱۶۶۱ position (GG vs. AA+AG), the AA genotype was more common in controls than in patients (adjusted P = ۰.۰۰۰۳; OR = ۰.۱۵, ۹۵% CI = ۰.۰۵۱ -۰.۴۲). The GCAT haplotype was also more prevalent in controls than in patients (adjusted P = ۰.۰۱; OR = ۰.۴۰, ۹۵% CI = ۰.۲۰-۰.۸۱). Furthermore, the ACGT/ACGT diplotype was more common in controls than in patients (P = ۰.۰۰۳۷; OR = ۰.۱۵, ۹۵% CI = ۰.۰۴-۰.۵۴). In addition, the ACGT/ACAT diplotype was more frequent in patients than controls (adjusted P =۰.۰۰۳; OR = ۲.۴۸, ۹۵% CI = ۱.۳۷- ۴.۵۰). Conclusions: Our results indicated that polymorphisms in CTLA-۴ 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.

Keywords:

CTLA-۴ gene Polymorphism , Haplotype analysis , Hepatitis C virus