Association of CTLA-4 and IL-4 polymorphisms in viral induced liver cancer

Abstract

Background Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer and is responsible for close to one million annual deaths globally. In Pakistan, HCC accounts for 10.7% of cancer incidence. Prior studies indicated an association between interleukin 4 (IL-4) and cytotoxic T lymphocyte protein 4 (CTLA-4) gene polymorphisms in many types of cancers, including HCC that are either hepatitis B virus (HBV)- or hepatitis C Virus (HCV)-induced. The association of IL-4 and CTLA-4 genetic polymorphisms with HCV-induced HCC is not yet determined in the Pakistani population. Therefore, this research is designed to investigate the implication of IL-4 and CTLA-4 gene polymorphisms by determining the association of IL-4 -590 C/T (rs2243250) and CTLA-4 + 49 A/G (rs231775) with HCC in Pakistan. Methods Different bioinformatics tools were employed to determine the pathogenicity of these polymorphisms. Samples were collected from HCV-induced HCC patients, followed by DNA extraction and ARMS-PCR analysis. Results The SNP analysis results indicated a positive association of IL-4 -590C/T and CTLA-4 + 49A/G gene polymorphisms with HCV-induced HCC in Pakistan. The CTLA-4 polymorphism might enhance therapeutic efficiency of HCC chemotherapy medicines. The IL-4 polymorphism might introduce new transcription factor binding site in IL-4 promoter region. Conclusion This study delineated risk factor alleles in CTLA-4 and IL-4 genes associated with HCV-mediated HCC among Pakistani patients that may have application to serve as genetic markers for pre- and early diagnosis and prognosis of HCC in HCV patients.

Detection of IL-1β, VEGF and IL-4 with their novel genetic variations in breast cancer patients

“…These results provide an interpretation for the decreased level of IL-4 in BC. Moreover, several polymorphisms related to IL-4 encoding gene were shown to be a cancer risk factor ( Ibrahimi et al, 2018 , Shabbir et al, 2022 , Safwat et al, 2022 ).…”

Investigation of UTR Variants by Computational Approaches Reveal Their Functional Significance in PRKCI Gene Regulation

“…SNPs are identified as the variations in genes that have large occurrence and proportion compared to other variations. SNPs, particularly, in the coding region have direct association with phenotype change [31,32]. However, in comparison to coding regions, most SNPs are located in the non-coding regions through GWAS [33].…”

PRKCE non-coding variants influence on transcription as well as translation of its gene

“…These variants modify important motifs in the region leading to an altered binding of regulatory proteins to the gene elements [ 62 ]. Further, these variants either pre-dispose an individual to a disease or reduces the disease risk [ 3 , 63 ]. Therefore, it is important to understand the disease mechanism at genetic level as well as protein level.…”

“…Such approaches have helped provide direction to research and save time, energy, and material and financial resources. Previously, pathogenic variants in CTLA4 and IL-4 genes were evaluated through this coupled approach [ 3 ].…”