Influence of cytotoxic T lymphocyte-associated antigen 4 polymorphisms on the outcomes of hepatitis B virus infection

Abstract

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates T-cell activation and Th1/Th2 cytokine production and is involved in the immune response against Hepatitis B virus (HBV) infection. To detect the association of the CTLA-4 gene polymorphisms with susceptibility to HBV infection a hospital-based case-control study was conducted. A total of 1,119 unrelated individuals were recruited. The CTLA-4 variants rs5742909, rs231775 and rs3087243 were genotyped via the TaqMan method in this cohort. A comparison with a chronic active hepatitis B group revealed that the SNP rs231775 exhibited significant susceptibility to HBV progression, with the highest odds ratio (OR) reaching 1.659 and P=0.009-0.049. Although an HBV clearance group was used as a control, results of the present study demonstrated an association of rs5742909 with viral persistence [OR=1.694, 95% confidence intervals (CI)=1.124-2.553 and P=0.012]. Subsequent analyses revealed risk haplotypes (C-A-A and T-A-G, for which the highest OR reached 1.865) compared with the protective haplotype C-G-G. Therefore, SNPs in the CTLA-4 gene may be associated with HBV progression and viral persistence which is consistent with its emerging role in the T regulatory cells in the pathogenesis of disease.

Single Nucleotide Polymorphisms of Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) and Susceptibility to Chronic Viral Hepatitis B and C Infections

“…The presence of the −319T allele of −319 C/T SNP is associated with greater promoter activity than the −319C allele, contributing to a greater expression of the CTLA-4 gene, representing a mechanism to inhibit the exaggerated cellular immune response (38) and contribute to hepatocellular damage in HBV and HCV infections (Figure 1A) (30,(39)(40)(41)(42). The −319T allele is associated with the likelihood of HBV persistence and susceptibility to progression of chronic liver damage, which is consistent with its emerging role in the T-regulatory cells in the pathogenesis of disease (31,43). Conversely, some studies report that the −319 C/T SNP was underrepresented in patients with chronic HBV infection compared with healthy controls, and that it was not associated with autoimmune liver disease (33).…”

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

“…Previous studies have provided evidence that an alternatively spliced mRNA of the CTLA-4 gene that lacks exon 3 is expressed in human, mouse, and rat immune cells (9,10) .The CTLA-4 gene is located on chromosome 2q33, the gene contains of four exons and three introns (11) . CTLA-4 gene encodes a 233 amino-acid protein (12) .There are approximately 100 SNPs have been reported in CTLA-4 gene (13) .These polymorphisms have been investigated for linkage with a number of human certain diseases (14) .The CTLA-4−319C/T polymorphism is associated with the HBV persistence and susceptibility to progression of chronic liver damage, which is consistent with its emerging role in the Tregulatory cells in the pathogenesis of disease (15) . Many studies were indicated an association between CTLA-4 -1722rs733618 and certain disease (16,17) , since this SNP is in the promoter region of the gene, it may alter the http://doi.org/10.36295/ASRO.2021.24533 DOI: 416 | P a g e transcriptional regulation of CTLA-4 (2) ,CTLA-4 haplotypes are important to determinant of HBV recovery, these haplotypes may alter the ability of CTLA-4 to down regulate the immune response (2) .…”

Polymorphisms rs231775 and rs5742909 CTLA-4 gene and their associative relations with chronic HBV infection in children

“…Это свидетельствовало о более высокой G-экспрессии гена CTLA-4 в условиях HBV-инфекции и указывало на избыточное вовлечение в патологических процесс активированных Т-клеток. Если учесть, что преобладающим иммунным ответом является активация Т-лимфоцитов, которые отвечают за высвобождение цитокинов и скоординированный лизис инфицированных клеток [14], то можно предположить о последствиях неправильной индукции и регуляции Т-клеток со стороны CTLA-4, формирующих в целом течение заболевания.…”