Genomic approaches to cardiac health: Assessing vitamin d receptor gene variations in coronary artery disease susceptibility within the one health framework

Abstract

Introduction: Coronary artery disease (CAD) is a complex, multifactorial disease. CAD is a cause of morbidity and mortality worldwide. Different studies from different countries have established the genetic association between CAD and vitamin D receptor gene polymorphism. Vitamin D receptor (VDR) binds with active form of vitamin D and play crucial role in regulating the transcription of many  genes and has significant impact on the morphology, proliferation, and growth of cardiac cells. Genetic variation in VDR gene such as  intronic and exonic polymorphism may results in altered structure and function of vitamin D receptor which disturb the binding of  vitamin D that may cause adverse effect in CAD. The study objective included, analyzing serum vitamin D levels and the association of intronic and exonic polymorphism in coronary artery disease patients and controls in order to examine its role towards the susceptibility  of disease condition

Materials & Methods: The study included 1016 Blood samples, 516 from coronary artery disease patients collected  (National Institute of Cardiovascular Diseases (NICVD), Pakistan) that were compared with 500 age and gender matched healthy controls.  Genomic DNA was extracted by standard phenol chloroform method. Amplification of targeted sequence was carried out  through allele specific polymerase chain reaction (AS-PCR). The PCR products were examined by agarose gel electrophoresis. The genetic  variations were confirmed by Sanger sequencing the and serum Vitamin D levels were assessed by using Enzyme Linked Immunosorbent  Assay (ELISA) for the quantification analysis between diseased and healthy subjects.

Result & Discussion: The presenting research has  focused primarily on human subjects, but Oral Presentation the implications of current findings extend far beyond human species. The  observed allelic variants for intronic and exonic polymorphism resulted successful amplification in amplified PCR products confirmed by  Sanger sequence. The sequence analyses confirmed both match and variant mismatches. The high frequency for heterozygous variation  has been observed in CAD patients showed significant association with exonic variation TaqI Polymorphism (P < 0.001). However, no association was found with intronic variation BsmI Polymorphism (P>0.05) between cases and controls. Serum vitamin D levels showed significantly lower levels in CAD patients compared to controls (P<0.001). Haplotype analysis on both SNPs showed the possible risk with  multiple haplotypes combination. The Linkage disequilibrium (LD) plot of SNPs was found in linkage for intronic and exonic polymorphisms in VDR gene. The results obtained might aid in disease surveillance and monitoring in an integrated manner to gain a better understanding of disease dynamics and to develop effective prevention and control strategies

Conclusion: This study may  represent a potential insight to consider clinical approach for better therapeutic intervention and management of the disease. The One  Health framework beckons not only to consider the genetic threads within human species but also to acknowledge the shared  vulnerabilities arising from our environment.