eNOS Gene Variants and Their Genetic Susceptibility Associated with Coronary Heart Disease
Abstract
Objective: Gene variations in the gene encoding endothelial nitric oxide synthase (eNOS) may impact the initiation of coronary heart disease (CHD). Insufficient production of nitric oxide (NO) is the most obvious cause of endothelial dysfunction. The aim of this study was to investigate polymorphisms in the eNOS genes G894T and T786C that influence the development of CHD.
Material and Methods: A total of 91 angiographically proven CHD subjects at the Department of Cardiology and Medicine and 91 controls at master health check, in the age group of 30-45 years were evaluated in this cross-sectional study. After overnight fasting blood samples were collected for evaluation of lipid profile by using Auto analyzer AU 480 and NO by Griess reaction, using Enzyme linked Immunosorbent assay. Polymerase Chain Reaction and Restriction Fragment Length Polymerization were used to amplify the eNOS gene, T786C, and G894T, respectively.
Results: A significant decrease in the serum level of NO was observed in CHD subjects compared to controls. In eNOS T786C polymorphism, the distribution of TC genotype (p-value=0.017) odds ratio (OR)=2.1 and minor C allele frequency (p-value=0.001). Additionally, for eNOS G894T polymorphism, the distribution of GT genotype (p-value=0.014) OR=2.03 and minor T allele frequency (p-value=0.001).
Conclusion: This study concludes that polymorphisms of the eNOS genes G894T and T786C could increase the risk of CHD.
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Roberts R, Stewart AF, Wells GA, Williams KA, Kavaslar N, McPherson R. Identifying genes for coronary artery disease: An idea whose time has come. Can J Cardiol 2007;23:7A-15.
Mohammad AM, Jehangeer HI, Shaikhow SK. Prevalence and risk factors of premature coronary artery disease in patients undergoing coronary angiography in Kurdistan, Iraq. BMC Cardiovascular Disorders 2015;15:155.
Eslami A, Mozaffary A, Derakhshan A, Azizi F, Khalili D, Hadaegh F. Sex-specific incidence rates and risk factors of premature cardiovascular disease. A long term follow up of the Tehran Lipid and Glucose Study. Int J Cardiol 2017;227:826-32.
Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012;33:829-37.
Jia Shi, Yi Yang, Anying Cheng, Gang Xu, Fan He. Metabolism of vascular smooth muscle cells in vascular diseases. Am J Physiol Heart Cir Physiol 2020; 319:H613-31.
Rossi GP, Cesari M, Zanchetta M, Colonna S, Maiolino G, Pedon L, Cavallin M, Maiolino P, Pessina AC. The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study. J Am Coll Cardiol 2003;41:930–7.
Zeng WP, Zhang R, Li R, Luo JF, Hu XF. Association of the endothelial nitric oxide synthase gene T-786C polymorphism with in-stent restenosis in Chinese nan patients with coronary artery disease treated with drug- eluting stent. PLoS One 2017;12:e0170964. doi:10.1371/journal.pone.0170964.
Miyamoto Y, Saito Y, Nakayama M, Shimasaki Y, Yoshimura T, Yoshimura M, et al. Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a -786T-->C mutation associated with coronary spastic angina. Hum Mol Genet 2000;9:2629-37.
Jousilahti P, Puska P, Vartiainen E, Pekkanen J, Tuomilehto J. Parental history of premature coronary heart disease: an independent risk factor of myocardial infarction. J Clin Epidemiol 1996;49:497-503.
Roncaglioni MC, Santoro L, D'Avanzo B, Negri E, Nobilli A, Ledda A, Pietropaolo F, Franzosi MG, La Vecchia C, Feruglio GA, Maseri A. Role of family history in patients with myocardial infarction. An Italian case-control study. Circulation 1992;85: 2065-72.
Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med 1994;330:1041-6.
Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol 2018;17:121.
Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 2012;10:4-18.
Cesari M, Kritchevsky SB, Atkinson HH, Penninx BW, Bari MD, Tract RO, et al. Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study. Am Heart J 2009;157:334.e1-8
Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med 2012;2012:918267. doi: 10.1155/2012/918267.
Watt J, Kennedy S, Ahmed N, Hayhurst J, McClure JD, Berry C, et al. The relationship between oxidised LDL, endothelial progenitor cells and coronary endothelial function in patients with CHD. Open Heart 2016;28;3:e000342.
Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. Int J Bio Sci 2013;9:1057-69.
Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kujiyama K, et al. T-786C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999;99:2864-70.
Wang XL, Wang J. Endothelial nitric oxide synthase gene sequence variations and vascular disease. Molecular genetic and metabolism 2000;70:241-51.
Han Y, Xu W, Zhang W, Liu N, Ji Y. T-786C Polymorphism in the Endothelial Nitric Oxide Synthase Gene Is Associated with Increased Risk of Coronary Artery Disease in a Chinese Population. Pharmacology 2010;85:211-6.
Miyamoto Y, Saito Y, Nakayama M, Shimasaki Y, Yoshimura T, Yoshimura M, et al. Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a -786T-->C mutation associated with coronary spastic angina. Hum Mol Genet 2000;9:2629-37.
Álvarez R, González P, Batalla A, Reguero JR, Iglesias-Cubero G, Hevia S, et al. Association between the NOS3 (−786 T/C) and the ACE (I/D) DNA Genotypes and Early Coronary Artery Disease. Nitric Oxide 2001;5:343-8.
Zigra AM, Rallidis LS, Anastasiou G, Merkouri E, Gialeraki A. eNOS gene variants and the risk of premature myocardial infarction. Dis Markers 2013;34:431-6.
Ghilardi G, Biondi ML, De Monti M, Bernini M, Turri O, Massaro F. Independent risk factor for moderat to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene. Clin Chem 2002;48:989-93.
Elakkad AM, Abou-Aisha K, Hassanein SI, Gad MZ. T-786C variation in the promoter sequence of human eNOS gene markedly influences its expression level. Drug Discov Ther 2017;11:193-7.
Kim IJ, Bae J, Lim SW, Cha DH, Cho HJ, Kim S, et al. Influence of endothelial nitric oxide synthase gene polymorphisms (−786T >C, 4a4b, 894G >T) in Korean patients with coronary artery disease. Thrombo Res 2007;119:579-85.
Salimi S, Naghavi A, Firoozrai M, Zandd H, Tavilani H, Nakhaee A, et al. Association of plasma nitric oxide concentration and endothelial nitric oxide synthase T-786C gene polymorphism in coronary artery disease. Pathophysiology 2012;19:157-62.
Srivastava K, Biswas UK, Narang R, Varghese JJ, Das N. Prevalence of eNOS Glu298Asp polymorphism in healthy volunteers from a region of Northern India. Community Genet 2005;8:180-3.
Parveen R, Parveen F, Kumar S, Kapoor A, Sinha N. Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review. PLoS ONE 2014;9:e113363.
Syed R, Biyabani MU, Prasad S, Deeba F, Jamil K. Evidence of association of a common variant of the endothelial nitric oxide gene polymorphism (Glu 298->Asp) to coronary artery disease in South Indian population. J Med Genet Genomics 2011;3:13-8.
Idrissi HH, Hmimecha W, Diakite B, Korchi F, Baghdadi D, et al. Association of G-894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms with susceptibility to myocardial infarction in Morocco. Meta Gene 2016;9:56-61.
Ben Ali M, Messaoudi S, Ezzine H, Mahjoub T. Contribution of eNOS variants to the genetic susceptibility of coronary artery disease in a Tunisian population. Genet Test Mol Biomarkers 2015;19:203-8.
Angeline T, Isabel W, Tsongalis GJ. Endothelial nitric oxide gene polymorphisms, nitric oxide production and coronary artery disease risk in a South Indian population. Exp Mol Pathol 2010;89:205–8.
Joshi MS, Mineo C, Shaul PW, Bauer JA. Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear. FASEB J 2007;21:2655-63.
Abdel-Aziz T, Mohamed R. Association of endothelial nitric oxide synthase gene polymorphisms with classical risk factors in development of premature coronary artery disease. Mol Bio Rep 2013;40:3065-71.
Isordia-Salas I, Leanos-Miranda A, Borrayo-Sanchez G. The Glu298ASP polymorphism of the endothelial nitric oxide synthase gene is associated with premature ST elevation myocardial infarction in Mexican population. Clin Chem Acta 2010;411:553-7.
Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007;87:315-424.
Saini V, Bhatnagar MK, Bhattacharjee J. Endothelial nitric oxide synthase Glu298Asp (G894T) gene polymorphism in coronary artery disease patients with type 2 diabetes mellitus. Diabetes Metab Syndr 2012;6:106-9.
Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci USA 2000; 97:2832-5.
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