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Current Pharmacogenomics and Personalized Medicine


ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Research Article

PCSK9 A/G (rs505151) Gene Polymorphism and its Expression at the Molecular Level in Patients with Coronary Artery Disease

Author(s): Kamna Srivastava*, Shelly Aggarwal, Rajiv Narang and Daman Saluja

Volume 19, Issue 2, 2022

Published on: 20 October, 2022

Page: [66 - 76] Pages: 11

DOI: 10.2174/1875692119666220930161000

Price: $65


Background: PCSK9 (Proprotein convertase subtilisin/kexin type 9) plays a key role in cholesterol homeostasis and Coronary artery disease (CAD). Many studies have extrapolated the association of the PCSK9 gene with low-density lipoprotein cholesterol (LDL-C) levels and CAD but with contradicting results. No such study is available stating the intergenotypic variations in the levels of expression of PCSK9 and LDL-C and their correlations with CAD risk factors in patients with CAD.

Objective: We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and its expression at mRNA and protein levels in patients with CAD. It also investigates how LDL-C, PCSK9, BMI, and systolic blood pressure (SBP) levels in patients with CAD and in healthy participants relate to the PCSK9 intergenotypic variation.

Methods: Angiographically confirmed CAD patients [n=250] and controls [n=250] were genotyped by PCR followed by RFLP techniques. Real-time PCR and Western Blot methods were used to investigate PCSK9's differential expression.

Results: Odds ratio being the index of association, revealed a statistically significant association of PCSK9 A/G (rs505151), A Vs G= 4.94 [1.37-7.79] polymorphism with CAD. In patients with the GG genotype, there is a correlation between higher PCSK9 gene expression and circulating LDL-C levels.

Conclusion: Our study shows a significant association of PCSK9 gene polymorphism with CAD. We also observed an increased expression of the PCSK9 gene in patients with the G allele. In our study, PCSK9 A/G (rs505151) gene and LDL-C emerged as independent risk factors. More follow-up research is required to determine whether upregulated PCSK9 gene expression can act as a prognostic marker for CAD.

Keywords: Coronary artery disease, genetic polymorphism, low-density lipoprotein receptor, proprotein convertase, subtilisin/kexin type 9, SBP, LDL-C.

Graphical Abstract
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