Association of CTLA-4 gene polymorphism and serum level of soluble CTLA-4 with chronic hepatitis C virus (HCV) infection

The World Health Organisation reports that approximately 130-170 million people worldwide are infected with hepatitis C virus (HCV) and more than 350,000 people die each year from HCV-related liver diseases. Even in the same geographical regions, different individuals vary greatly in developing HCV infection, pointing to the role of individual genetic factors in HCV. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein that plays a key role in the negative regulation of T cell immune responses and is found mostly on the surface of cells responsible for the activation and regulation of T cells. It is thought that a single nucleotide polymorphism (SNP) in the gene encoding this protein may affect CTLA-4 activity and thus immune response to HCV. In this study, we aimed to investigate the relationship between CTLA-4+49A/G single nucleotide gene polymorphisms (SNPs) in the CTLA-4 gene and soluble CTLA-4 (sCTLA-4) levels with HCV infection and HCV viral load. A total of 120 patients with confirmed HCV infection who were admitted to Baghdad Digestive System and Liver Teaching Hospital between June 2023 and June 2024 and 60 age- and sex-matched healthy individuals without HCV infection were included in the study as control group. Demographic data were collected through direct interviews. Five millilitres of venous blood was collected from all participants. Liver enzymes were measured spectrophotometrically. A commercial ELISA kit was used to determine the serum level of sCTLA-4. Genomic DNA of the individuals was extracted from whole blood, the gene fragment corresponding to the CTLA-4+49A/G SNP was amplified using the T-ARMS-PCR method with four primers and genotyping was performed. It was found that serum sCTLA-4 levels were significantly increased in patients with HCV infection and positively correlated with ALT and HCV viral load. The AA genotype and A allele of CTLA-4+49A/G gene polymorphism could be accepted as a risk factor for HCV infection. The AA genotype of this polymorphism was also associated with a relative increase in HCV viral load reflection through the activity of CTLA-4 protein and concomitant T-cell inhibition