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

Abstract

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 PCSK9 gene with low density lipoprotein cholesterol (LDL-C) levels and CAD but with contradicting results. There is no such study 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 level in patients with CAD. Additionally, it is investigated how the levels of LDL-C, PCSK9, BMI, and systolic blood pressure (SBP) 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 PCSK9 gene in patients with G allele. In our study, PCSK9 A/G (rs505151) gene and LDL-C emerged as independent risk factors. To determine whether upregulated PCSK9 gene expression can act as a prognostic marker for CAD, more follow-up research is required.