Polymorphic Variant rs11206510 in PCSK9 and Risk of Coronary Artery Disease in Bulgarians
DOI:
https://doi.org/10.2478/AMB-2023-0003Keywords:
PCSK9, polymorphic variant, coronary artery disease, BulgariansAbstract
Objective
The aim of this study was to investigate the potential association of rs11206510 in PCSK9 gene with coronary artery disease (CAD) and myocardial infarction (MI) in Bulgarians.
Materials and Methods
The current analysis included 261 patients with angiographically documented CAD (153 with MI and 108 without MI) and 496 population – based controls. Genomic DNA was extracted from venous blood samples. The selected polymorphism was genotyped by TaqMan SNP Genotyping Assay. The genotype and allele frequencies were compared between cases and controls using χ2 test.
Results
In this study, the presence of the T allele of rs11206510 in the PCSK9 gene was found to be associated with elevated risk for MI in patients with already existing myocardial ischemia (allele T, OR1.78,CI95:1.16-2.73, p = 0.007). The result was enhanced in the male subgroup (allele T, OR1.74, CI95:1.02-2.96, p = 0.038). Also, we found reduced risk of CAD (without MI) for T allele (OR0.70, CI95:0.49-0.99, p = 0.04). This trend was stronger in the male subgroup (OR0.56, CI95:0.35-0.90, p = 0.02). There was not any relationship of the studied genetic variant with the levels of total cholesterol, triglycerides, low density lipoproteins and high-density lipoproteins, or with systolic and diastolic blood pressure values.
Conclusion
Our study found a difference in the frequencies of rs11206510 genotypes and alleles in the PCSK9 gene between cases and controls, and the relationship of the investigated polymorphism to the risk of cardiac injury in the Bulgarian population was demonstrated. Further investigations with a larger number of cases and controls will be needed in order to evaluate a possible association between this variant and CAD/MI in Bulgarians.
References
Fitzgerald K et al. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. N Engl J Med, 2017, 376(1):41-51.
Abifadel M et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet, 2003,34(2):154-6.
Qiu C et al. What is the impact of PCSK9 rs505151 and rs11591147 polymorphisms on serum lipids level and cardiovascular risk: a meta-analysis. Lipids Health Dis, 2017,16(1):111.
Cai G et al. The associations between proprotein convertase subtilisin/kexin type 9 E670G polymorphism and the risk of coronary artery disease and serum lipid levels: a meta-analysis. Lipids Health Dis, 2015,14:149.
Adi D et al. Relationships between genetic polymorphisms of E670G in PCSK9 gene and coronary artery disease: a metaanalysis. Int J Clin Exp Med, 2015, 8(8):13251-8.
Thygesen K, Alpert J, Jaffe A, et al. Third universal definition of myocardial infarction. Circulation. 2012;126;2020-35.
Thygesen K, Alpert J, Jaffe A, et al. Fourth universal definition of myocardial infarction (2018). European Heart Journal. 2019; 40: 237-69.
Mach F, Baigent C, Catapano A, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Tak Force for the management of Dyslipidaemias of the European Society of Cardiology {ESC} and European Atherosclerosis Society (EAS). European Heart Journal. 2020; 41: 111-88.
Peterson AS, Fong LG, Young SG. PCSK9 function and physiology. J Lipid Res, 2008,49(7):1595-9.6.
Stein R, Ferrari F, Scolari F, Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights. Curr Cardiol Rep, 2019,21(8):68.7.
Mega JL et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet, 2015,385(9984): 2264-2271.8.
McPherson R, Tybjaerg-Hansen. Generics of Coronary Artery Disease. Circulation Research. 2016; 118: 564-78.
Findley A, Richards A, Petrini C, et al. Interpreting coronary artery disease risk through gene-environment interactions in gene regulation. Genetics. 2019; 213: 651-63.
Findley A, Monziani A, Richards A, et al. Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions. eLife. 2021; 10: e67077.
Zhu L, Ji X, Jiang L, et al. Utility of genetic variants to predict prognosis in coronary artery disease patietns receiving statin treatment. Int J Clin Exp Pathol. 2017; 10: 8795-8803.
Kathiresan, S. et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009; 41, 334-41.
Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidleines for the diagnosis and management of chronic coronary syndromes: The Task Force for diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2020; 41: 407-77.
Ibanez B, James S, Agewall S, et al. 2017 ESC Guidlienes for the management of acute myocardial infarction in patients presenting with CT segment elevation: The Task Force for the management of acute Myocardial infarction in patients presenting with ST – segment elevation of the European Society of Cardiology.Eur Heart J, 2018; 39: 119-77.
Collet J, Thiele H, Barbato E, et al. 2020 ESC Guideliens for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). 2021; 42: 1289-1367
Lloyd-Jones DM et al. Lifetime risk of coronary heart disease by cholesterol levels at selected ages. Arch Intern Med, 2003,163(16): 1966-72.9.
Kathiresan S et al. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med Genet, 2007,8 Suppl 1: S17.10.
Zhou Li, He M, Mo Z, et al. A genome wide association study identifies common variants associated with lipid levels in the Chinese population. PLoS One. 2013; 8(12): e82420.
Teslovich TM et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature, 2010.,466(7307):707-13. 11.
Guella I et al. Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. J Lipid Res, 2010,51(11):3342-9.12.
Willer CJ et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet, 2008,40(2):161-9.13.
Schunkert H et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet, 2011,43(4):333-8.14.
Waterworth DM et al. Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arterioscler Thromb Vasc Biol, 2010,30(11):2264-76. 15.
Kathiresan S et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet, 2009,41(1):56-65. 16.
Reilly MP et al. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet, 2011,377(9763):383-92.17.
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