Association of ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with Coronary Artery Disease (CAD)

Jyotdeep Kour Raina,Rakesh Kumar Panjaliya,Vikas Dogra,Parvinder Kumar,Ashok Bakaya,Minakashee Sharma

doi:10.1186/s12872-020-01618-7

Jyotdeep Kour Raina, Rakesh Kumar Panjaliya + Show 4 more

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https://doi.org/10.1186/s12872-020-01618-7

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Abstract

BackgroundCoronary artery disease (CAD) is a complex disease resulting from the cumulative and interactive effects of large number of genes along with environmental exposure. Therefore, the present study was envisaged as an effort to study the association of candidate genes ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with the risk of CAD, targeting the populations of Jammu (JandK).MethodA total of 400 confirmed CAD patients and 400 healthy controls were enrolled for the present study. Genotyping was done by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).ResultsESR1 gene (rs9340799) polymorphism was found to be associated with CAD in all the genetic models. The haplotype analysis of ESR1 (rs2234693 and rs9340799) gene revealed that C-G haplotype was conferring approximately 5-fold risk and T-A haplotype was adding 1.4-fold risk towards the disease. ‘T’ allele of MTHFR rs1801133 SNP was observed to be responsible for development of CAD in our study population (p < 0.0001). In case of MTHFR (rs1801133 and rs2274976) gene, the haplotype T-G was observed to confer 4.7-fold risk towards CAD whereas haplotype C-G provided nearly a 1.7 fold protection towards development of CAD. For MS gene, rs185087 was also found to be associated with CAD in a co-dominant (p = 0.003 and p = 0.03), dominant (p = 0.001) and allelic models (p = 0.001). The gene-gene interaction revealed strong epistasis between single nucleotide polymorphisms (SNPs), ESR1 rs9340799 and MTHFR rs2274976. Furthermore, the dendrogram for gene-environment dataset indicated moderately synergistic interaction between CETP rs708272 and physical inactivity.ConclusionIn the study under reference, a significant association of ESR1-XbaI (rs9340799), MTHFR C677T (rs1801133) and MS A2756G (rs185087) gene polymorphisms with the susceptibility of CAD in the population of Jammu region (JandK) has been observed.

Highlights

Coronary artery disease (CAD) is a complex disease resulting from the cumulative and interactive effects of large number of genes along with environmental exposure
ESR1 gene polymorphism was found to be associated with CAD in all the genetic models
A significant difference was observed between Pulse pressure (PP) (53.73 ± 16.77 vs 41.58 ± 8.12, p < 0.0001) and Pulse rate (PR) (82.11 ± 12.23 vs 74.41 ± 4.91, p < 0.0001) values in patients and controls as in metabolic variables like Total Cholesterol (TC), TG, LDL and high-density lipoprotein (HDL) levels among the study participants

Summary

Introduction

Coronary artery disease (CAD) is a complex disease resulting from the cumulative and interactive effects of large number of genes along with environmental exposure. The present study was envisaged as an effort to study the association of candidate genes ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with the risk of CAD, targeting the populations of Jammu (JandK). The plausible justification for increase in CVD cases in India is that presently the nation is facing rapid urbanisation resulting in changing lifestyle. Coronary artery disease (CAD) is a major CVD phenotype being noticed in Indians. It is estimated that Asian Indians constitute a fifth of the global population with CAD [2]. CAD is a complex disease resulting from the cumulative and interactive effects of large number of genes along with environmental exposure

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