Low CPNE3 expression is associated with risk of acute myocardial infarction: A feasible genetic marker of acute myocardial infarction in patients with stable coronary artery disease
Abstract
Background: Gene COPINE III may be related to a phosphoprotein with intrinsic kinase activity and
belongs to an unconventional kinase family. The CPNE3 gene may be used as a biomarker for assess- ment of occurrence and prognosis of various tumors.
Methods: Peripheral blood was collected from 87 stable coronary artery disease (CAD) patients and 91 acute myocardial infarction (AMI) patients. Real-time quantitative polymerase chain reaction test and the western blot method were adopted to measure expression quantity of CPNE3 gene at the mRNA level and the protein level.
Results: The expression of the CPNE3 gene in peripheral blood of AMI patients was significantly lower than those in peripheral blood of stable CAD patients. Low expression of CPNE3 gene was found to be unrelated to level of fasting blood glucose and serum blood lipid of patients, quantity of cardiac troponin and time of onset but was found to be correlated to the Gensini score for coronary artery. When the ex- pression of CPNE3 gene at the mRNA level in peripheral blood was used as the criterion for diagnosing AMI, its sensitivity, specificity, positive predictive value and negative predictive value were 69%, 64.8%, 68.6% and 65.2%, respectively.
Conclusions: Compared to stable CAD patients, AMI patients have a lower expression of CPNE3 gene in their peripheral blood. Patients who have low CPNE3 expression in peripheral blood are more likely to suffer from AMI than those with stable CAD. Low expression of CPNE3 gene serves as an potential independent risk factor of AMI.
Keywords: CPNE3 geneacute myocardial infarctionstable coronary artery diseaseindependent riskperipheral bloodgenetic marker
References
- Shah PK. Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovasc Dis. 2002; 44(5): 357–368.
- Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011; 473(7347): 317–325.
- Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation. 2005; 111(25): 3481–3488.
- Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003; 290(7): 898–904.
- Kraus WE. Genetic approaches for the investigation of genes associated with coronary heart disease. Am Heart J. 2000; 140(4): S27–S35.
- Aziz H, Zaas A, Ginsburg GS. Peripheral blood gene expression profiling for cardiovascular disease assessment. Genomic Med. 2007; 1(3-4): 105–112.
- Elashoff MR, Wingrove JA, Beineke P, et al. Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. 2011; 4: 26.
- Maneerat Y, Prasongsukarn K, Benjathummarak S, et al. Increased alpha-defensin expression is associated with risk of coronary heart disease: a feasible predictive inflammatory biomarker of coronary heart disease in hyperlipidemia patients. Lipids Health Dis. 2016; 15: 117.
- Caudell EG, Caudell JJ, Tang CH, et al. Characterization of human copine III as a phosphoprotein with associated kinase activity. Biochemistry. 2000; 39(42): 13034–13043.
- Perestenko PV, Pooler AM, Noorbakhshnia M, et al. Copines-1, -2, -3, -6 and -7 show different calcium-dependent intracellular membrane translocation and targeting. FEBS J. 2010; 277(24): 5174–5189.
- Lin Hc, Zhang Fl, Geng Q, et al. Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC. J Proteome Res. 2013; 12(7): 3423–3433.
- Mo W, Zhang J, Li X, et al. Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer. PLoS One. 2013; 8(2): e56592.
- Cohen OS, Mccoy SY, Middleton FA, et al. Transcriptomic analysis of postmortem brain identifies dysregulated splicing events in novel candidate genes for schizophrenia. Schizophr Res. 2012; 142(1-3): 188–199.
- Thygesen K, Alpert J, Jaffe A, et al. Third Universal Definition of Myocardial Infarction. Journal of the American College of Cardiology. 2012; 60(16): 1581–1598.
- Montalescot G, Sechtem U, Achenbach S, et al. Task Force Members, ESC Committee for Practice Guidelines, Document Reviewers. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34(38): 2949–3003.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25(4): 402–408.
- Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. J Clin Lipidol. 2014; 8(5): 473–488.
- Chamberlain JJ, Rhinehart AS, Shaefer CF, et al. Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2016; 164(8): 542–552.
- Heinrich C, Keller C, Boulay A, et al. Copine-III interacts with ErbB2 and promotes tumor cell migration. Oncogene. 2010; 29(11): 1598–1610.
- Desta L, Jernberg T, Spaak J, et al. Heart failure with normal ejection fraction is uncommon in acute myocardial infarction settings but associated with poor outcomes: a study of 91,360 patients admitted with index myocardial infarction between 1998 and 2010. Eur J Heart Fail. 2016; 18(1): 46–53.
- Murakami H, Igarashi K, Igarashi Y, et al. [Influence of number of citizens greater than 50 years of age on prevalence of acute myocardial infarction: epidemiological study of Sapporo residents]. J Cardiol. 2007; 50(3): 167–174.
- Rich MW, Bosner MS, Chung MK, et al. Is age an independent predictor of early and late mortality in patients with acute myocardial infarction? Am J Med. 1992; 92(1): 7–13.
- Bayturan O, Kapadia S, Nicholls SJ, et al. Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol. J Am Coll Cardiol. 2010; 55(24): 2736–2742.
- Chhatriwalla AK, Nicholls SJ, Wang TH, et al. Low levels of low-density lipoprotein cholesterol and blood pressure and progression of coronary atherosclerosis. J Am Coll Cardiol. 2009; 53(13): 1110–1115.
- Kronmal RA, McClelland RL, Detrano R, et al. Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2007; 115(21): 2722–2730.
- Pekkanen J, Linn S, Heiss G, et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med. 1990; 322(24): 1700–1707.
- Bayturan O, Tuzcu EM, Uno K, et al. Comparison of rates of progression of coronary atherosclerosis in patients with diabetes mellitus versus those with the metabolic syndrome. Am J Cardiol. 2010; 105(12): 1735–1739.
- Perk J, De Ba, Gohlke H, et al. European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts)]. Giornale italiano di cardiologia. 2013; 14(5): 328–92.
- Frey P, Waters DD, DeMicco DA, et al. Impact of smoking on cardiovascular events in patients with coronary disease receiving contemporary medical therapy (from the Treating to New Targets [TNT] and the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] trials). Am J Cardiol. 2011; 107(2): 145–150.
- Otaki Y, Gransar H, Berman DS, et al. Impact of family history of coronary artery disease in young individuals (from the CONFIRM registry). Am J Cardiol. 2013; 111(8): 1081–1086.
- Huang G, Zhao JL, Du H, et al. Coronary score adds prognostic information for patients with acute coronary syndrome. Circ J. 2010; 74(3): 490–495.