Evaluation of cytotoxic T- lymphocyte antigen-4 (CTLA-4) polymorphisms and soluble CTLA-4 (sCTLA-4) in chronic hepatitis B virus infection

Abstract

The cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory receptors expressed transiently on CD4+ and CD8+ T cell and constitutively on CD4+CD25+ T-regulator (T-reg) cells. CTLA-4 gene encoded two different protein forms: soluble CTLA-4 (sCTLA-4) and full length CTLA-4 (flCTLA-4). Treg cells were demonstrated to be a prominent source of sCTLA-4.Single nucleotide polymorphisms (SNPs) occurring on the CTLA-4 gene can modify the ability to control the proliferation of T-lymphocytes, thereby impacting the persistence or progression of chronic hepatitis B (HBV) infections.The present study aimed to determine whether the polymorphisms in CTLA-4gene, (CTLA-4-1722T/Crs733618, CTLA-4-319C/T rs5742909and CTLA-4-1661A/G rs4553808) are associated with the progression or persistence of chronic HBV, and the impact of sCTLA-4 on chronic HBV disease in Iraq.Ninety patients with chronic (complicated and uncomplicated) HBV and 30 healthy control were recruited. A blood sample and genomic DNA were collected from all patients, the sCTLA-4 in patients and healthy control are detected by ELISA assay. The CTLA-4-gene was detected by DNA sequencing after amplification of the genes by Conventional PCR with specific primers.All the genotypes for CTLA-4 polymorphisms were analyzed for linkage disequilibrium. There was very high linkage disequilibrium between rs4553808 with rs733618, and in moderate LD with rs420909 suggesting that alleles of these SNPs variants are likely to be inherited together.