一氧化氮合酶和血管紧张素转换酶基因多态性与冠心病相关性研究进展

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (2): 222-228.

一氧化氮合酶和血管紧张素转换酶基因多态性与冠心病相关性研究进展

房超¹, 曾慧², 周宏灏¹, 刘昭前¹

¹中南大学临床药理研究所,湖南省遗传药理学重点实验室,长沙 410078,湖南;
²长沙卫生职业学院,长沙 410100,湖南

收稿日期:2012-09-12 修回日期:2012-09-12 发布日期:2013-02-28
通讯作者: 刘昭前, 通信作者, 男,博士,教授,博士生导师,研究方向:遗传药理学与药物基因组学。 Tel: 0731-84805380 E-mail: liuzhaoqian63@126.com
作者简介:房超,男,硕士,研究方向:遗传药理学与药物基因组学。 Tel: 0731-84805380 E-mail: fangchao412@yeah.net
基金资助:
国家高技术研究发展计划(863计划)(2012AA02A517); 国家自然科学基金(81173129); 湖南省自然科学创新群体基金(12JJ7006)

Research progress on relationship between eNOS and ACE gene polymorphisms and coronary heart disease

FANG Chao¹, ZENG Hui², ZHOU Hong-Hao¹, LIU Zhao-Qian¹

¹Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Genetic Pharmacology, Changsha 410078, Hunan, China;
²The Health Vocational College of Changsha, Changsha 410100, Hunan, China

Received:2012-09-12 Revised:2012-09-12 Published:2013-02-28

摘要/Abstract

摘要： 冠状动脉性心脏病(coronary heart disease,CHD)是全球关注的公共卫生问题,是影响人类健康和寿命的关键疾病之一。一氧化氮合酶(eNOS)和血管紧张素转换酶(ACE)是体内对心血管系统具有重要作用的两种酶。基因组学研究发现eNOS和ACE基因多态性与CHD的发生具有相关性,本文就eNOS和ACE基因多态性与冠心病的易感性进行综述。

关键词: 冠心病, 一氧化氮合酶, 血管紧张素转换酶, 基因多态性

Abstract: Coronary heart disease (CHD) is one of the most serious disease that affects human health and life. It is also a public health problem concerned worldwide. The nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) have an important influence on the cardiovascular system in vivo. The genomics study found that the eNOS and ACE gene polymorphism correlate with the occurrence of CHD. This article covers the progress between eNOS and ACE gene polymorphism and coronary heart disease susceptibility.

Key words: Coronary heart disease, Endothelial nitric oxide synthase, Angiotensin converting enzyme, Gene polymorphism

中图分类号:

R968

房超, 曾慧, 周宏灏, 刘昭前. 一氧化氮合酶和血管紧张素转换酶基因多态性与冠心病相关性研究进展[J]. 中国临床药理学与治疗学, 2013, 18(2): 222-228.

FANG Chao, ZENG Hui, ZHOU Hong-Hao, LIU Zhao-Qian. Research progress on relationship between eNOS and ACE gene polymorphisms and coronary heart disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(2): 222-228.

参考文献

[1] Kimura H,Esumi H.Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis[J]. Acta Biochimica Polonica, 2003, 50(1): 49-59.
[2] Kuhlencordt PJ, Gyurko R, Han F, et al.Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice[J]. Circulation, 2001, 104(4): 448-454.
[3] Nadaud S, Bonnardeaux A, Lathrop M, et al.Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene[J]. Biochem Biophys Res Commun, 1994, 198(3): 1027-1033.
[4] Hall AV, Antoniou H, Wang Y, et al.Structural organization of the human neuronal nitric oxide synthase gene (NOS1)[J]. J Biol Chem, 1994, 269(52): 33082-33090.
[5] Marsden PA, Heng HH, Duff CL, et al.Localization of the human gene for inducible nitric oxide synthase (NOS2) to chromosome 17q11.2-q12[J]. Genomics, 1994, 19(1): 183-185.
[6] Kroncke KD, Fehsel K, Kolb-Bachofen V.Nitric oxide: cytotoxicity versus cytoprotection- how, why, when, and where[J]? Nitric Oxide, 1997, 1(2): 107-120.
[7] McIntyre M, Dominiczak AF. Nitric oxide and cardiovascular disease[J]. Postgrad Med J, 1997, 73(864): 630-634.
[8] Garnaud PE, Koetsier M, Ost TW, et al.Redox properties of the isolated flavin mononucleotide- and flavin adenine dinucleotide-binding domains of neuronal nitric oxide synthase[J]. Biochemistry, 2004, 43(34): 11035-11044.
[9] Sagami I, Daff S, Shimizu T.Intra-subunit and inter-subunit electron transfer in neuronal nitric-oxide synthase: effect of calmodulin on heterodimer catalysis[J]. J Biol Chem, 2001, 276(32): 30036-30042.
[10] Karupiah G, Chen JH, Nathan CF, et al.Identification of nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection[J]. J Virol, 1998, 72(9): 7703-7706.
[11] Dawson VL, Dawson TM.Nitric oxide in neurodegeneration[J]. Prog Brain Res, 1998, 118: 215-229.
[12] Beall CM, Laskowski D, Strohl KP, et al.Pulmonary nitric oxide in mountain dwellers[J]. Nature, 2001, 414(6862): 411-412.
[13] Thorn CF, Klein TE, Altman RB.PharmGKB summary: very important pharmacogene information for angiotensin-converting enzyme[J]. Pharmacogenet Genomics, 2010, 20(2): 143-146.
[14] Siragy HM, Carey RM.The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats[J]. J Clin Invest, 1997, 100(2): 264-269.
[15] Moncada S, Higgs EA.The discovery of nitric oxide and its role in vascular biology[J]. Br J Pharmacol, 2006, 147(Suppl 1): S193-201.
[16] Tesauro M, Thompson WC, Rogliani P, et al.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[J]. Proc Natl Acad Sci U S A, 2000, 97(6): 2832-2835.
[17] Loscalzo J, Welch G.Nitric oxide and its role in the cardiovascular system[J]. Prog Cardiovasc Dis, 1995, 38(2): 87-104.
[18] Lefer AM.Nitric oxide: nature's naturally occurring leukocyte inhibitor[J]. Circulation, 1997, 95(3): 553-554.
[19] Morishita R, Gibbons GH, Ellison KE, et al.Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme[J]. J Clin Invest, 1994, 94(3): 978-984.
[20] Singer DR, Missouris CG, Jeffery S.Angiotensin-converting enzyme gene polymorphism. What to do about all the confusion[J]. Circulation, 1996, 94(3): 236-239.
[21] Saini V, Bhatnagar MK, Bhattacharjee J.Association of endothelial dysfunction with endothelin, nitric oxide and eNOS Glu298Asp gene polymorphism in coronary artery disease[J]. Dis Markers, 2011, 31(4): 215-222.
[22] Wang CL, Hsu LA, Ko YS, et al.Lack of association between the Glu298Asp variant of the endothelial nitric oxide synthase gene and the risk of coronary artery disease among Taiwanese[J]. J Formos Med Assoc, 2001, 100(11): 736-740.
[23] Rahimi Z, Nourozi-Rad R.Association of endothelial nitric oxide synthase gene variant (G894T) with coronary artery disease in Western Iran[J]. Angiology, 2012, 63(2): 131-137.
[24] Min BW, Na JY, Juhng SW, et al.A polymorphism (G894T) in eNOS increases the risk of coronary atherosclerosis rather than intracranial atherosclerosis in Koreans[J]. Acta Neurol Belg, 2010, 110(3): 255-262.
[25] Fatini CF, Sofi, Gensini F, et al.Influence of eNOS gene polymorphisms on carotid atherosclerosis[J]. Eur J Vasc Endovasc Surg, 2004, 27(5): 540-544.
[26] Fatini C, Sofi F, Sticchi E, et al.Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes[J]. Am Heart J, 2004, 147(3): 516-521.
[27] Firouzabadi N, Tajik N, Bahramali E, et al.Association of angiotensin-converting enzyme polymorphism with coronary artery disease in Iranian patients with unipolar depression[J]. Clin Biochem, 2012, 45(16/17): 1347-1352.
[28] Shafiee SM, Firoozrai M, Salimi S, et al.Angiotensin converting enzyme DD genotype not associated with increased risk of coronary artery disease in the Iranian population[J]. Pathophysiology, 2010, 17(3): 163-167.
[29] Abd El-Aziz TA, Hussein YM, Mohamed RH, et al. Renin-angiotensin system genes polymorphism in Egyptians with premature coronary artery disease[J]. Gene, 2012, 498(2): 270-275.
[30] Pandey U, Kumari R, Nath B, et al.Association of angiotensin-converting enzyme, methylene tetrahydrofolate reductase and paraoxonase gene polymorphism and coronary artery disease in an Indian population[J]. Cardiol J, 2011, 18(4): 385-394.
[31] Hamelin BA, Zakrzewski-Jakubiak M, Robitaille NM, et al.Increased risk of myocardial infarction associated with angiotensin-converting enzyme gene polymorphism is age dependent[J]. J Clin Pharmacol, 2011, 51(9): 1286-1292.
[32] Kitsios G, Zintzaras E.ACE (I/D) polymorphism and response to treatment in coronary artery disease: a comprehensive database and meta-analysis involving study quality evaluation[J]. BMC Med Genet, 2009, 10: 50.
[33] Zintzaras E, Raman G, Kitsios G, et al.Angiotensin-converting enzyme insertion/deletion gene polymorphic variant as a marker of coronary artery disease: a meta-analysis[J]. Arch Intern Med, 2008, 168(10): 1077-1089.
[34] Zhou L, Xi B, Wei Y, et al.Meta-analysis of the association between the insertion/deletion polymorphism in ACE gene and coronary heart disease among the Chinese population[J]. J Renin Angiotensin Aldosterone Syst, 2012, 13(2): 296-304.