(Circulation. 1996;94:708-712.)
© 1996 American Heart Association, Inc.
Articles |
the Departments of Cardiology (N.J.S.), Medicine and Therapeutics (N.J.S., K.L.W.), and Ophthalmology (J.R.T.), University of Leicester (United Kingdom); and the Department of Cardiology (L.O., K.C.), Royal Hallamshire Hospital, Sheffield, United Kingdom.
Correspondence to Dr N.J. Samani, Department of Cardiology, Clinical Sciences Wing, Glenfield Hospital, Groby Rd, Leicester LE3 9QP, UK.
Background The ACE gene is characterized by a polymorphism based on the presence (insertion [I]) or absence (deletion [D]) within intron 16 of a 287-basepair alu repeat sequence, resulting in three genotypes. Subsequent studies have produced conflicting findings. To further evaluate the association of the ACE I/D genotype with MI risk, we carried out a meta-analysis of all the published studies.
Methods and Results In total, 15 studies containing 3394 MI cases and 5479 control subjects were analyzed. The overall distribution of genotypes in the control subjects was 22.7% II, 49.0% ID, and 28.3% DD. The mean odds ratio for MI for DD versus ID/II genotypes across all studies was 1.26 (95% CI, 1.15, 1.39; P<.0001). Pairwise odds ratios were 1.36 (95% CI, 1.19, 1.55) for DD and II, 1.24 (95% CI, 1.11, 1.38) for DD and ID, and 1.09 (95% CI, 0.96, 1.23) for ID and II. The relative risk appeared to be increased in Japanese populations (2.55; 95% CI, 1.75, 3.70).
Conclusions Within the limitations of the available data, the meta-analysis therefore supports an association of the ACE D allele with MI risk and strengthens the justification for further evaluation in appropriately powered studies.
Key Words: genes myocardial infarction enzymes angiotensin risk factors meta-analysis
This article has been cited by other articles:
![]() |
E. Zintzaras, G. Raman, G. Kitsios, and J. Lau Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphic Variant as a Marker of Coronary Artery Disease: A Meta-analysis Arch Intern Med, May 26, 2008; 168(10): 1077 - 1089. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. A. Iakoubova, C. H. Tong, C. M. Rowland, T. G. Kirchgessner, B. A. Young, A. R. Arellano, D. Shiffman, M. S. Sabatine, H. Campos, C. J. Packard, et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 435 - 443. [Abstract] [Full Text] [PDF] |
||||
![]() |
T.-H. Lin, H.-C. Chiu, Y.-T. Lee, H.-M. Su, W.-C. Voon, H.-W. Liu, W.-T. Lai, and S.-H. Sheu Association Between Functional Polymorphisms of Renin-Angiotensin System, Left Ventricular Mass, and Geometry Over 4 Years in a Healthy Chinese Population Aged 60 Years and Older J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2007; 62(10): 1157 - 1163. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Tiroch, W. Koch, N. von Beckerath, A. Kastrati, and A. Schomig Heme oxygenase-1 gene promoter polymorphism and restenosis following coronary stenting Eur. Heart J., April 2, 2007; 28(8): 968 - 973. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Bilici, M. S. Ulgen, H. Nazaroglu, O. Ozturk, F. Ekici, C. Akgul, and B. Alan The Effect of ACE Gene Polymorphisms on Doppler Blood Flow Parameters of Carotid and Brachial Arteries in Patients With Myocardial Infarction Angiology, January 1, 2007; 57(6): 681 - 685. [Abstract] [PDF] |
||||
![]() |
W. Koch, P. Hoppmann, A. Pfeufer, A. Schomig, and A. Kastrati Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population Eur. Heart J., November 1, 2006; 27(21): 2524 - 2529. [Abstract] [Full Text] [PDF] |
||||
![]() |
Prepared by: British Cardiac Society, British Hype JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice Heart, December 1, 2005; 91(suppl_5): v1 - v52. [Full Text] [PDF] |
||||
![]() |
D. J. Lehmann, M. Cortina-Borja, D. R. Warden, A. D. Smith, K. Sleegers, J. A. Prince, C. M. van Duijn, and P. G. Kehoe Large Meta-Analysis Establishes the ACE Insertion-Deletion Polymorphism as a Marker of Alzheimer's Disease Am. J. Epidemiol., August 15, 2005; 162(4): 305 - 317. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. BEDNARSKA-MAKARUK, M. RODO, C. MARKUSZEWSKI, A. ROZENFELD, M. SWIDERSKA, B. HABRAT, and H. WEHR POLYMORPHISMS OF APOLIPOPROTEIN E AND ANGIOTENSIN-CONVERTING ENZYME GENES AND CAROTID ATHEROSCLEROSIS IN HEAVY DRINKERS Alcohol Alcohol., July 1, 2005; 40(4): 274 - 282. [Abstract] [Full Text] [PDF] |
||||
![]() |
F A Sayed-Tabatabaei, A F C Schut, A Arias Vasquez, A M Bertoli-Avella, A Hofman, J C M Witteman, and C M van Duijn Angiotensin converting enzyme gene polymorphism and cardiovascular morbidity and mortality: the Rotterdam Study J. Med. Genet., January 1, 2005; 42(1): 26 - 30. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Cascorbi, M. Paul, and H. K. Kroemer Pharmacogenomics of heart failure - focus on drug disposition and action Cardiovasc Res, October 1, 2004; 64(1): 32 - 39. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Slowik, W. Turaj, T. Dziedzic, A. Haefele, J. Pera, M. T. Malecki, L. Glodzik-Sobanska, P. Szermer, D. A. Figlewicz, and A. Szczudlik DD genotype of ACE gene is a risk factor for intracerebral hemorrhage Neurology, July 27, 2004; 63(2): 359 - 361. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Humphries, P. M. Ridker, and P. J. Talmud Genetic Testing for Cardiovascular Disease Susceptibility: A Useful Clinical Management Tool or Possible Misinformation? Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 628 - 636. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Petrovic, D. Bregar, B. Guzic-Salobir, E. Skof, M. Span, R. Terzic, M. G. Petrovic, I. Keber, M. Letonja, M. Zorc, et al. Sex Difference in the Effect of ACE-DD Genotype on the Risk of Premature Myocardial Infarction Angiology, March 1, 2004; 55(2): 155 - 158. [Abstract] [PDF] |
||||
![]() |
J. S. Elkins, V. C. Douglas, and S. C. Johnston Alzheimer disease risk and genetic variation in ACE: A meta-analysis Neurology, February 10, 2004; 62(3): 363 - 368. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Fernandez, J. J. Rodriguez Reguero, and P. Gonzalez Angiotensin-converting enzyme polymorphism (I/D) and coronary heart disease in young adults J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1864 - 1864. [Full Text] [PDF] |
||||
![]() |
V. A. Cameron and B. R. Palmer Angiotensin-converting enzyme polymorphism (I/D) and coronary heart disease in young adults: Reply J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1864 - 1864. [Full Text] [PDF] |
||||
![]() |
S Ye, S Dhillon, R Seear, L Dunleavey, L B Day, W Bannister, I N M Day, and I Simpson Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis Heart, October 1, 2003; 89(10): 1195 - 1199. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. B. M. Da Cruz, G. Oliveira, M. Taufer, N. F. Leal, C. H. Schwanke, L. Glock, Y. Moriguchi, and E. H. Moriguchi Angiotensin I-Converting Enzyme Gene Polymorphism in Two Ethnic Groups Living in Brazil's Southern Region: Association With Age J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2003; 58(9): M851 - 856. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Aucella, M. Margaglione, M. Vigilante, G. Gatta, E. Grandone, M. Forcella, M. Ktena, A. De Min, G. Salatino, D. A. Procaccini, et al. PAI-1 4G/5G and ACE I/D gene polymorphisms and the occurrence of myocardial infarction in patients on intermittent dialysis Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1142 - 1146. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. S. Jacoby and D. J. Rader Renin-Angiotensin System and Atherothrombotic Disease: From Genes to Treatment Arch Intern Med, May 26, 2003; 163(10): 1155 - 1164. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. R. Palmer, A. P. Pilbrow, T. G. Yandle, C. M. Frampton, A. M. Richards, M. G. Nicholls, and V. A. Cameron Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction J. Am. Coll. Cardiol., March 5, 2003; 41(5): 729 - 736. [Abstract] [Full Text] [PDF] |
||||
![]() |
M Hamon, S Fradin, A Denizet, E Filippi-Codaccioni, G Grollier, and R Morello Prospective evaluation of the effect of an angiotensin I converting enzyme gene polymorphism on the long term risk of major adverse cardiac events after percutaneous coronary intervention Heart, March 1, 2003; 89(3): 321 - 325. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. L Ruberg and J. Loscalzo Prothrombotic determinants of coronary atherothrombosis Vascular Medicine, November 1, 2002; 7(4): 289 - 299. [Abstract] [PDF] |
||||
![]() |
D. R. Dengel, M. D. Brown, R. E. Ferrell, T. H. Reynolds IV, and M. A. Supiano Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults Physiol Genomics, October 29, 2002; 11(2): 73 - 80. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Montgomery, S. Humphries, and S. Danilov Is genotype or phenotype the better tool for investigating the role of ACE in human cardiovascular disease? Eur. Heart J., July 2, 2002; 23(14): 1083 - 1086. [Full Text] [PDF] |
||||
![]() |
B.-M. Taute, C. Glaser, R. Taute, and H. Podhaisky Progression of Atherosclerosis in Patients with Peripheral Arterial Disease as a Function of Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism Angiology, July 1, 2002; 53(4): 375 - 382. [Abstract] [PDF] |
||||
![]() |
R. A. Hegele SNP Judgments and Freedom of Association Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1058 - 1061. [Full Text] [PDF] |
||||
![]() |
F. G. H. van der Kleij, P. E. de Jong, R. H. Henning, D. de Zeeuw, and G. Navis Enhanced Responses of Blood Pressure, Renal Function, and Aldosterone to Angiotensin I in the DD Genotype Are Blunted by Low Sodium Intake J. Am. Soc. Nephrol., April 1, 2002; 13(4): 1025 - 1033. [Abstract] [Full Text] |
||||
![]() |
J. M. Hagberg, S. D. McCole, M. D. Brown, R. E. Ferrell, K. R. Wilund, A. Huberty, L. W. Douglass, and G. E. Moore ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women J Appl Physiol, March 1, 2002; 92(3): 1083 - 1088. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Swynghedauw Susceptibility-conferring polymorphic genotypes in cardiovascular multifactorial syndromes Eur. Heart J., February 2, 2002; 23(4): 271 - 273. [Full Text] [PDF] |
||||
![]() |
M. Egger, S. Ebrahim, and G. D. Smith Where now for meta-analysis? Int. J. Epidemiol., February 1, 2002; 31(1): 1 - 5. [Full Text] [PDF] |
||||
![]() |
W. R. P. Agema, J. W. Jukema, S. N. Pimstone, and J. J. P. Kastelein Genetic aspects of restenosis after percutaneous coronary interventions;towards more tailored therapy Eur. Heart J., November 2, 2001; 22(22): 2058 - 2074. [PDF] |
||||
![]() |
E. J. Balkestein, J. A. Staessen, J.-G. Wang, J. J. van der Heijden-Spek, L. M. Van Bortel, C. Barlassina, G. Bianchi, E. Brand, S.-M. Herrmann, and H. A. Struijker-Boudier Carotid and Femoral Artery Stiffness in Relation to Three Candidate Genes in a White Population Hypertension, November 1, 2001; 38(5): 1190 - 1197. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. B. Harrap and S. Petrou Utility of genetic approaches to common cardiovascular diseases Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H1 - H6. [Full Text] [PDF] |
||||
![]() |
T. Mannami, T. Katsuya, S. Baba, N. Inamoto, K. Ishikawa, J. Higaki, T. Ogihara, and J. Ogata Low Potentiality of Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism as a Useful Predictive Marker for Carotid Atherogenesis in a Large General Population of a Japanese City : The Suita Study Stroke, June 1, 2001; 32(6): 1250 - 1256. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Rodriguez-Perez, F. Rodriguez-Esparragon, O. Hernandez-Perera, A. Anabitarte, A. Losada, A. Medina, E. Hernandez, D. Fiuza, O. Avalos, C. Yunis, et al. Association of angiotensinogen m235t and a(-6)g gene polymorphisms with coronary heart disease with independence of essential hypertension: the procagene study J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1536 - 1542. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Petrovic, M. Zorc, V. Kanic, and B. Peterlin Interaction Between Gene Polymorphisms of Renin-angiotensin System and Metabolic Risk Factors in Premature Myocardial Infarction Angiology, April 1, 2001; 52(4): 247 - 252. [Abstract] [PDF] |
||||
![]() |
G. P. Rossi, S. Taddei, A. Virdis, L. Ghiadoni, G. Albertin, S. Favilla, I. Sudano, A. C. Pessina, and A. Salvetti Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction Hypertension, February 1, 2001; 37(2): 293 - 300. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Batalla, R. Alvarez, J. R. Reguero, S. Hevia, G. Iglesias-Cubero, V. Alvarez, A. Cortina, P. Gonzalez, M. M. Celada, A. Medina, et al. Synergistic Effect between Apolipoprotein E and Angiotensinogen Gene Polymorphisms in the Risk for Early Myocardial Infarction Clin. Chem., December 1, 2000; 46(12): 1910 - 1915. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. K. Naber, J. Husing, U. Wolfhard, R. Erbel, and W. Siffert Interaction of the ACE D Allele and the GNB3 825T Allele in Myocardial Infarction Hypertension, December 1, 2000; 36(6): 986 - 989. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Prasad, S. Narayanan, M. A. Waclawiw, N. Epstein, and A. A. Quyyumi The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1579 - 1586. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. Wierzbicki, M. Lambert-Hammill, P. J. Lumb, and M. A. Crook Renin-Angiotensin System Polymorphisms and Coronary Events in Familial Hypercholesterolemia Hypertension, November 1, 2000; 36(5): 808 - 812. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Koch, A. Kastrati, J. Mehilli, C. Bottiger, N. von Beckerath, and A. Schomig Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Not Associated With Restenosis After Coronary Stent Placement Circulation, July 11, 2000; 102(2): 197 - 202. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Prasad, S. Narayanan, S. Husain, F. Padder, M. Waclawiw, N. Epstein, and A. A. Quyyumi Insertion-Deletion Polymorphism of the ACE Gene Modulates Reversibility of Endothelial Dysfunction With ACE Inhibition Circulation, July 4, 2000; 102(1): 35 - 41. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Rankinen, B. Wolfarth, J.-A. Simoneau, D. Maier-Lenz, R. Rauramaa, M. A. Rivera, M. R. Boulay, Y. C. Chagnon, L. Perusse, J. Keul, et al. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status J Appl Physiol, May 1, 2000; 88(5): 1571 - 1575. [Abstract] [Full Text] [PDF] |
||||
![]() |
C Fatini, R Abbate, G Pepe, B Battaglini, F Gensini, G Ruggiano, G.F Gensini, and R Guazzelli Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms Eur. Heart J., April 2, 2000; 21(8): 633 - 638. [Abstract] [PDF] |
||||
![]() |
O. Samuelsson, P.-O. Attman, R. Larsson, H. Mulec, L. Rymo, L. Weiss, and A. Ricksten Angiotensin I-converting enzyme gene polymorphism in non-diabetic renal disease Nephrol. Dial. Transplant., April 1, 2000; 15(4): 481 - 486. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Agerholm-Larsen, B. G. Nordestgaard, and A. Tybjarg-Hansen ACE Gene Polymorphism in Cardiovascular Disease : Meta-Analyses of Small and Large Studies in Whites Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 484 - 492. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Olivieri, E. Trabetti, S. Grazioli, C. Stranieri, S. Friso, D. Girelli, C. Russo, P. F. Pignatti, G. Mansueto, and R. Corrocher Genetic Polymorphisms of the Renin-Angiotensin System and Atheromatous Renal Artery Stenosis Hypertension, November 1, 1999; 34(5): 1097 - 1100. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. T. Heijmans, R. G. J. Westendorp, D. L. Knook, C. Kluft, and P. E. Slagboom Angiotensin I-converting enzyme and plasminogen activator inhibitor-1 gene variants: risk of mortality and fatal cardiovascular disease in an elderly population-based cohort J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1176 - 1183. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Okamura, M. Ohishi, H. Rakugi, T. Katsuya, Y. Yanagitani, S. Takiuchi, Y. Taniyama, K. Moriguchi, H. Ito, Y. Higashino, et al. Pharmacogenetic Analysis of the Effect of Angiotensin-Converting Enzyme Inhibitor on Restenosis After Percutaneous Transluminal Coronary Angioplasty Angiology, October 1, 1999; 50(10): 811 - 822. [Abstract] [PDF] |
||||
![]() |
K. F. Hilgers, M. R. W. Langenfeld, M. Schlaich, R. Veelken, and R. E. Schmieder 1166 A/C Polymorphism of the Angiotensin II Type 1 Receptor Gene and the Response to Short-Term Infusion of Angiotensin II Circulation, September 28, 1999; 100(13): 1394 - 1399. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Pfohl, M. Koch, S. Prescod, K.K. Haase, H.U. Haring, and K.R. Karsch Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study Eur. Heart J., September 2, 1999; 20(18): 1318 - 1325. [Abstract] [PDF] |
||||
![]() |
R. R. Taylor, C. D. S. Mamotte, K. Fallon, and F. M. van Bockxmeer Elite athletes and the gene for angiotensin-converting enzyme J Appl Physiol, September 1, 1999; 87(3): 1035 - 1037. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Hung, B. M. McQuillan, M. Nidorf, P. L. Thompson, and J. P. Beilby Angiotensin-Converting Enzyme Gene Polymorphism and Carotid Wall Thickening in a Community Population Arterioscler. Thromb. Vasc. Biol., August 1, 1999; 19(8): 1969 - 1974. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. M Pinto and W. H van Gilst The ACE gene polymorphism: the good, the bad and the ugly Cardiovasc Res, July 1, 1999; 43(1): 23 - 24. [Full Text] [PDF] |
||||
![]() |
E. M Lonn and S. Yusuf Evidence based cardiology: Emerging approaches in preventing cardiovascular disease BMJ, May 15, 1999; 318(7194): 1337 - 1341. [Full Text] |
||||