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

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