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

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.