Abstract
Background
Calmodulin 1 (CALM1) mutations are involved in the development of coronary artery disease (CAD). However, the relationship of CALM1 rs3179089 polymorphism with CAD is unknown.
Objective
This study aimed to identify the relationship of CALM1 rs3179089 polymorphism with CAD susceptibility, CALM1 expression, blood pressure, blood glucose, blood coagulation and serum lipid levels of CAD patients.
Methods
550 CAD patients and 550 control subjects were genotyped for CALM1 using Sequenom MassARRAY technology. CALM1 expression level was measured by quantitative real time polymerase chain reaction (qRT-PCR).
Results
CALM1 mRNA expression was higher in CAD patients than that in control subjects (P < 0.001). CAD patients with CC genotype had higher CALM1 mRNA expression level than control subjects with CC genotype (P = 0.006). Genotypic frequency of rs3179089 was different between male patients of CAD and control subjects (P = 0.045). Rs3179089 polymorphism was related to CAD risk of males in recessive model (P = 0.039). Moreover, rs3179089 polymorphism was associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), and D-Dimer (D-D) level of patients with CAD in recessive model (P = 0.013 for SBP; P = 0.034 for DBP; P = 0.004 for FPG; P = 0.046 for D-D). In addition, rs3179089 polymorphism was correlated with low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) serum levels of patients with CAD in both addictive (P = 0.025 for LDL-C; P = 0.001 for TC) and recessive models (P = 0.001 for LDL-C; P = 0.001 for TC).
Conclusion
CALM1 expression is associated with development of CAD. CALM1 rs3179089 polymorphism affects CAD susceptibility in males, and blood pressure, blood glucose, blood coagulation and serum lipid of CAD patients.
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Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Adam AM, Rehan A, Waseem N, Iqbal U, Saleem H, Ali MA, Shaikh AT, Godil A (2017) Prevalence of conventional risk factors and evaluation of baseline indices among young and elderly patients with coronary artery disease. J Clin Diagn Res 11:OC34–OC39
Agiannitopoulos K, Bakalgianni A, Marouli E, Zormpa I, Manginas A, Papamenzelopoulos S, Lamnissou K (2016) Gender specificity of a genetic variant of androgen receptor and risk of coronary artery disease. J Clin Lab Anal 30:204–207
Ahmed AM, Hersi A, Mashhoud W, Arafah MR, Abreu PC, Al Rowaily MA, Al-Mallah MH (2017) Cardiovascular risk factors burden in Saudi Arabia: the Africa Middle East Cardiovascular Epidemiological (ACE) study. J Saudi Heart Assoc 29:235–243
Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM (2005) Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res 97:1314–1322
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Bers DM (2004) Macromolecular complexes regulating cardiac ryanodine receptor function. J Mol Cell Cardiol 37:417–429
Boczek NJ, Gomez-Hurtado N, Ye D, Calvert ML, Tester DJ, Kryshtal D, Hwang HS, Johnson CN, Chazin WJ, Loporcaro CG et al (2016) Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT Syndrome-associated calmodulin missense variant, E141G. Circ Cardiovasc Genet 9:136–146
Budde T, Meuth S, Pape HC (2002) Calcium-dependent inactivation of neuronal calcium channels. Nat Rev Neurosci 3:873–883
Cai G, Shi G, Xue S, Lu W (2017) The atherogenic index of plasma is a strong and independent predictor for coronary artery disease in the Chinese Han population. Medicine (baltimore) 96:e8058
Chiang SM, Ueng KC, Yang YS (2020) Gender differences in variables associated with dipeptidyl peptidase 4 genetic polymorphisms in coronary artery disease. Adv Clin Exp Med 29:1181–1186
Chin D, Means AR (2000) Calmodulin: a prototypical calcium sensor. Trends Cell Biol 10:322–328
Ciampa EJ, Welch RC, Vanoye CG, George AL Jr (2011) KCNE4 juxtamembrane region is required for interaction with calmodulin and for functional suppression of KCNQ1. J Biol Chem 286:4141–4149
Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, Papagiannis J, Feldkamp MD, Rathi SG, Kunic JD et al (2013) Calmodulin mutations associated with recurrent cardiac arrest in infants. Circulation 127:1009–1017
Dadi PK, Vierra NC, Ustione A, Piston DW, Colbran RJ, Jacobson DA (2014) Inhibition of pancreatic beta-cell Ca2+/calmodulin-dependent protein kinase II reduces glucose-stimulated calcium influx and insulin secretion, impairing glucose tolerance. J Biol Chem 289:12435–12445
Daffara V, Verdoia M, Rolla R, Nardin M, Marino P, Bellomo G, Carriero A, De Luca G (2017) Impact of polymorphism rs7041 and rs4588 of Vitamin D Binding Protein on the extent of coronary artery disease. Nutr Metab Cardiovasc Dis 27:775–783
Gu L, Huang J, Li J, Huang S, Li M, Gong L, Li T, Su L (2018) Association of CALM1 rs3179089 polymorphism with Ischemic stroke in Chinese Han population. Neuromolecular Med 20:271–279
Hemal K, Pagidipati NJ, Coles A, Dolor RJ, Mark DB, Pellikka PA, Hoffmann U, Litwin SE, Daubert MA, Shah SH et al (2016) Sex differences in demographics, risk factors, presentation, and noninvasive testing in stable outpatients with suspected coronary artery disease: insights from the PROMISE trial. JACC Cardiovasc Imaging 9:337–346
Hokimoto S, Tabata N, Akasaka T, Arima Y, Kaikita K, Morita K, Kumagae N, Oniki K, Nakagawa K, Ogawa H (2015) Gender differences in impact of CYP2C19 polymorphism on development of coronary artery disease. J Cardiovasc Pharmacol 65:148–152
Huang Y, Hui Q, Gwinn M, Hu YJ, Quyyumi AA, Vaccarino V, Sun YV (2021) Sexual differences in genetic predisposition of coronary artery disease. Circ Genom Precis Med 14:e003147
Joseph JS, Ayeleso AO, Mukwevho E (2017) Role of exercise-induced calmodulin protein kinase (CAMK)II activation in the regulation of omega-6 fatty acids and lipid metabolism genes in rat skeletal muscle. Physiol Res. https://doi.org/10.33549/physiolres.933509
Kavousi M, Desai CS, Ayers C, Blumenthal RS, Budoff MJ, Mahabadi AA, Ikram MA, van der Lugt A, Hofman A, Erbel R et al (2016) Prevalence and prognostic implications of coronary artery calcification in low-risk women: a meta-analysis. JAMA 316:2126–2134
Kibos A, Guerchicoff A (2011) Susceptibility genes for coronary heart disease and myocardial infarction. Acute Card Care 13:136–142
Li DP, Zhou JJ, Zhang J, Pan HL (2017) CaMKII regulates synaptic NMDA receptor activity of hypothalamic presympathetic neurons and sympathetic outflow in hypertension. J Neurosci 37(44):10690–10699
Liu Z, Pericak-Vance MA, Goldschmidt-Clermont P, Seo D, Wang L, Rundek T, Beecham GW (2017) Coronary collateralization shows sex and racial-ethnic differences in obstructive artery disease patients. PLoS One 12:e0183836
Luke MM, Kane JP, Liu DM, Rowland CM, Shiffman D, Cassano J, Catanese JJ, Pullinger CR, Leong DU, Arellano AR et al (2007) A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler Thromb Vasc Biol 27:2030–2036
Mack M, Gopal A (2014) Epidemiology, traditional and novel risk factors in coronary artery disease. Cardiol Clin 32:323–332
Mahata SK, Kiranmayi M, Mahapatra NR (2017) Catestain: a master regulator of cardiovascular functions. Curr Med Chem 25:1352–1374
Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S (2019) A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol 234:16812–16823
Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3:e442
Naji DH, Tan C, Han F, Zhao Y, Wang J, Wang D, Fa J, Li S, Chen S, Chen Q et al (2017) Significant genetic association of a functional TFPI variant with circulating fibrinogen levels and coronary artery disease. Mol Genet Genomics 293:119–128
Nica AC, Dermitzakis ET (2013) Expression quantitative trait loci: present and future. Philos Trans R Soc Lond B Biol Sci 368:20120362
Ono M, Yano M, Hino A, Suetomi T, Xu X, Susa T, Uchinoumi H, Tateishi H, Oda T, Okuda S et al (2010) Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca(2+) release in heart failure. Cardiovasc Res 87:609–617
Paquette M, Dufour R, Baass A (2017) Scavenger receptor LOX1 genotype predicts coronary artery disease in patients with familial hypercholesterolemia. Can J Cardiol 33:1312–1318
Reed GJ, Boczek NJ, Etheridge SP, Ackerman MJ (2015) CALM3 mutation associated with long QT syndrome. Heart Rhythm 12:419–422
Schooling CM, Luo S, Au Yeung SL, Thompson DJ, Karthikeyan S, Bolton TR, Mason AM, Ingelsson E, Burgess S (2018) Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: a Mendelian randomization investigation. Int J Cardiol 267:171–176
Silbernagel G, Rein P, Saely CH, Engelberger RP, Willenberg T, Do DD, Kucher N, Baumgartner I, Drexel H (2015) Prevalence of type 2 diabetes is higher in peripheral artery disease than in coronary artery disease patients. Diab Vasc Dis Res 12:146–149
van den Hoogen PC, Feskens EJ, Nagelkerke NJ, Menotti A, Nissinen A, Kromhout D (2000) The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group. N Engl J Med 342:1–8
Van Petegem F, Lobo PA, Ahern CA (2012) Seeing the forest through the trees: towards a unified view on physiological calcium regulation of voltage-gated sodium channels. Biophys J 103:2243–2251
Vassilakopoulou V, Calver BL, Thanassoulas A, Beck K, Hu H, Buntwal L, Smith A, Theodoridou M, Kashir J, Blayney L et al (2015) Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease. Biochim Biophys Acta 1850:2168–2176
Winsvold BS, Bettella F, Witoelar A, Anttila V, Gormley P, Kurth T, Terwindt GM, Freilinger TM, Frei O, Shadrin A et al (2017) Shared genetic risk between migraine and coronary artery disease: a genome-wide analysis of common variants. PLoS ONE 12:e0185663
Yamaguchi N, Xu L, Pasek DA, Evans KE, Meissner G (2003) Molecular basis of calmodulin binding to cardiac muscle Ca(2+) release channel (ryanodine receptor). J Biol Chem 278:23480–23486
Yano M, Yamamoto T, Ikemoto N, Matsuzaki M (2005) Abnormal ryanodine receptor function in heart failure. Pharmacol Ther 107:377–391
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81660741; Grant No. 81573756).
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All authors contributed to the study conception and design. This study is supervised by LG. Material preparation, data collection and analysis were performed by JH, SH, JL, ML, LG, TL. The first draft of the manuscript was written by JH and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Jingyan Huang, Siyun Huang, Jinhong Li, Minhua Li, Lin Gong, Tongshun Li, Lian Gu declare that they have no competing interests.
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Approval was obtained from the ethics committee of the First Affiliated Hospital of Guangxi University of Chinese Medicine. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
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Huang, J., Huang, S., Li, J. et al. CALM1 rs3179089 polymorphism might contribute to coronary artery disease susceptibility in Chinese male: a case–control study. Genes Genom 44, 415–423 (2022). https://doi.org/10.1007/s13258-021-01144-6
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DOI: https://doi.org/10.1007/s13258-021-01144-6