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.
[http://dx.doi.org/10.1038/ng1161] [PMID: 12730697]
[http://dx.doi.org/10.1074/jbc.M409699200] [PMID: 15358785]
[http://dx.doi.org/10.1074/jbc.M708098200] [PMID: 18039658]
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.02.006] [PMID: 19249440]
[http://dx.doi.org/10.1086/507488] [PMID: 16909389]
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.04.006] [PMID: 22683120]
[http://dx.doi.org/10.1002/humu.20882] [PMID: 19191301]
[http://dx.doi.org/10.1056/NEJMoa1500858] [PMID: 25773607]
[http://dx.doi.org/10.1371/journal.pone.0101502] [PMID: 24992666]
[http://dx.doi.org/10.1161/CIRCGENETICS.108.828467] [PMID: 20031607]
[http://dx.doi.org/10.1016/j.jacc.2005.01.051] [PMID: 15893176]
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.06.023] [PMID: 19619878]
[http://dx.doi.org/10.1515/CCLM.2009.032] [PMID: 19191720]