Association Analysis of Single Nucleotide Polymorphisms (SNPs) in Core Promoter Region of m6A Writer Protein in Cardiovascular Disease

Ayesha Faryal

Authors

Ayesha Faryal COMSATS University Islamabad, Department of Biochemistry and Molecular Biology, Islamabad, Pakistan https://orcid.org/0009-0009-1434-2953

Keywords:

Cardiovascular disease (CVD), Single nucleotide polymorphism (SNP), N6-methyladenosine (m6A).

Abstract

Cardiovascular diseases (CVD) are a major cause of morbidity and fatality across the world. Coronary plaque progression and fragile plaque characteristics have been associated with CVD. Several risk factors linked to CVD are smoking, diabetes, age, rheumatoid arthritis, obesity, HDL, LDL, cholesterol and hypertension etc. Along with environmental factors, many genetic factors contribute towards the onset and progression of this disease. For genetic information moving from DNA to protein, RNA serves as an unavoidable connecting connection. Epitranscriptomics has been proposed to play an important role in controlling different functions of RNA to various physiological processes of a cell. The most predominant modification in eukaryotic cells is m⁶A which is regulated by a number of regulated proteins named generally as readers, writers and erasers. Single nucleotide polymorphism (SNP) in the promoter region is known to be involved in altering affinity for transcription factors resulting in variable gene expression. Keeping in view the importance of genetic variation in the form of SNPs, the present study was conducted to dissect the role A>C polymorphism in the promoter region of m6A writer gene KIAA1429 (rs3133659) and its correlation with CVD. In this study, blood samples were taken from hospitals of Rawalpindi and Islamabad, DNA was extracted. Polymorphism was studied through tetra-primer ARMS-PCR. Biochemical analysis from cases and controls shows a significant association of cholesterol, HDL, LDL and SBP in CVD (p<0.05). Comparison of genotypic and allelic frequencies using chi-square test z-test and odds ratio was done by Pearson and fischer model respectively. Results of the statistical analysis demonstrated that there were significant differences (p<0.05) in frequency distribution among cases and control. These results reflect that the rs3133659 A>, polymorphism in KIAA1429 correlates with CVD. Findings of this study are needed to be verified further with a large sample size to explore the role of this polymorphism in the aetiology of CVD in the population of Pakistan

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