Abstract
OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. DESIGN: Consecutive sample. SETTING: University hospital. SUBJECTS: 141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. MAIN OUTCOME MEASURES: Left ventricular variables were measured for all patients. The ACE and AT1R genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the AT1R genotypes. RESULTS: A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) g/m2; P < 0.003). However, no influence of ACE and AT1R polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the AT1R CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and AT1R gene polymorphisms on left ventricular function and mass was found. CONCLUSIONS: These data do not support an association of the ACE and AT1R genotypes on left ventricular hypertrophy in white patients with normal coronary arteries.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bonnardeaux A., Davies E., Jeunemaitre X., Féry I., Charru A., Clauser E., Tiret L., Cambien F., Corvol P., Soubrier F. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension. 1994 Jul;24(1):63–69. doi: 10.1161/01.hyp.24.1.63. [DOI] [PubMed] [Google Scholar]
- Cambien F., Poirier O., Lecerf L., Evans A., Cambou J. P., Arveiler D., Luc G., Bard J. M., Bara L., Ricard S. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992 Oct 15;359(6396):641–644. doi: 10.1038/359641a0. [DOI] [PubMed] [Google Scholar]
- Costerousse O., Allegrini J., Lopez M., Alhenc-Gelas F. Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J. 1993 Feb 15;290(Pt 1):33–40. doi: 10.1042/bj2900033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dahlöf B., Pennert K., Hansson L. Regression of left ventricular hypertrophy--a meta-analysis. Clin Exp Hypertens A. 1992;14(1-2):173–180. doi: 10.3109/10641969209036180. [DOI] [PubMed] [Google Scholar]
- Devereux R. B., Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1977 Apr;55(4):613–618. doi: 10.1161/01.cir.55.4.613. [DOI] [PubMed] [Google Scholar]
- Fogarty D. G., Maxwell A. P., Doherty C. C., Hughes A. E., Nevin N. C. ACE gene typing. Lancet. 1994 Apr 2;343(8901):851–851. doi: 10.1016/s0140-6736(94)92050-8. [DOI] [PubMed] [Google Scholar]
- Hamon M., Bauters C., Amant C., McFadden E. P., Helbecque N., Lablanche J. M., Bertrand M. E., Amouyel P. Relation between the deletion polymorphism of the angiotensin-converting enzyme gene and late luminal narrowing after coronary angioplasty. Circulation. 1995 Aug 1;92(3):296–299. doi: 10.1161/01.cir.92.3.296. [DOI] [PubMed] [Google Scholar]
- Iwai N., Ohmichi N., Nakamura Y., Kinoshita M. DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation. 1994 Dec;90(6):2622–2628. doi: 10.1161/01.cir.90.6.2622. [DOI] [PubMed] [Google Scholar]
- Kennedy J. W., Reichenbach D. D., Baxley W. A., Dodge H. T. Left ventricular mass. A comparison of angiocardiographic measurements with autopsy weight. Am J Cardiol. 1967 Feb;19(2):221–223. doi: 10.1016/0002-9149(67)90536-x. [DOI] [PubMed] [Google Scholar]
- Kennedy J. W., Reichenbach D. D., Baxley W. A., Dodge H. T. Left ventricular mass. A comparison of angiocardiographic measurements with autopsy weight. Am J Cardiol. 1967 Feb;19(2):221–223. doi: 10.1016/0002-9149(67)90536-x. [DOI] [PubMed] [Google Scholar]
- Kennedy J. W., Trenholme S. E., Kasser I. S. Left ventricular volume and mass from single-plane cineangiocardiogram. A comparison of anteroposterior and right anterior oblique methods. Am Heart J. 1970 Sep;80(3):343–352. doi: 10.1016/0002-8703(70)90099-2. [DOI] [PubMed] [Google Scholar]
- Kupari M., Perola M., Koskinen P., Virolainen J., Karhunen P. J. Left ventricular size, mass, and function in relation to angiotensin-converting enzyme gene polymorphism in humans. Am J Physiol. 1994 Sep;267(3 Pt 2):H1107–H1111. doi: 10.1152/ajpheart.1994.267.3.H1107. [DOI] [PubMed] [Google Scholar]
- Lacroix D., Nader M. A., Savoye C., Klug D., Logier R., Kacet S., Lekieffre J. Determination of left ventricular mass in systemic hypertension: comparison of standard and signal averaged electrocardiography. Br Heart J. 1995 Sep;74(3):277–281. doi: 10.1136/hrt.74.3.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindpaintner K., Lee M., Larson M. G., Rao V. S., Pfeffer M. A., Ordovas J. M., Schaefer E. J., Wilson A. F., Wilson P. W., Vasan R. S. Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass. N Engl J Med. 1996 Apr 18;334(16):1023–1028. doi: 10.1056/NEJM199604183341604. [DOI] [PubMed] [Google Scholar]
- Marian A. J., Yu Q. T., Workman R., Greve G., Roberts R. Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. Lancet. 1993 Oct 30;342(8879):1085–1086. doi: 10.1016/0140-6736(93)92064-z. [DOI] [PubMed] [Google Scholar]
- Morgan H. E., Baker K. M. Cardiac hypertrophy. Mechanical, neural, and endocrine dependence. Circulation. 1991 Jan;83(1):13–25. doi: 10.1161/01.cir.83.1.13. [DOI] [PubMed] [Google Scholar]
- Paxton W. G., Runge M., Horaist C., Cohen C., Alexander R. W., Bernstein K. E. Immunohistochemical localization of rat angiotensin II AT1 receptor. Am J Physiol. 1993 Jun;264(6 Pt 2):F989–F995. doi: 10.1152/ajprenal.1993.264.6.F989. [DOI] [PubMed] [Google Scholar]
- Pfeffer M. A., Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990 Apr;81(4):1161–1172. doi: 10.1161/01.cir.81.4.1161. [DOI] [PubMed] [Google Scholar]
- RACKLEY C. E., DODGE H. T., COBLE Y. D., Jr, HAY R. E. A METHOD FOR DETERMINING LEFT VENTRICULAR MASS IN MAN. Circulation. 1964 May;29:666–671. doi: 10.1161/01.cir.29.5.666. [DOI] [PubMed] [Google Scholar]
- Raynolds M. V., Bristow M. R., Bush E. W., Abraham W. T., Lowes B. D., Zisman L. S., Taft C. S., Perryman M. B. Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet. 1993 Oct 30;342(8879):1073–1075. doi: 10.1016/0140-6736(93)92061-w. [DOI] [PubMed] [Google Scholar]
- Reichek N., Devereux R. B. Left ventricular hypertrophy: relationship of anatomic, echocardiographic and electrocardiographic findings. Circulation. 1981 Jun;63(6):1391–1398. doi: 10.1161/01.cir.63.6.1391. [DOI] [PubMed] [Google Scholar]
- Rigat B., Hubert C., Alhenc-Gelas F., Cambien F., Corvol P., Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990 Oct;86(4):1343–1346. doi: 10.1172/JCI114844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schunkert H., Dzau V. J., Tang S. S., Hirsch A. T., Apstein C. S., Lorell B. H. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest. 1990 Dec;86(6):1913–1920. doi: 10.1172/JCI114924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schunkert H., Hense H. W., Holmer S. R., Stender M., Perz S., Keil U., Lorell B. H., Riegger G. A. Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med. 1994 Jun 9;330(23):1634–1638. doi: 10.1056/NEJM199406093302302. [DOI] [PubMed] [Google Scholar]
- Soubrier F., Alhenc-Gelas F., Hubert C., Allegrini J., John M., Tregear G., Corvol P. Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9386–9390. doi: 10.1073/pnas.85.24.9386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takayanagi R., Ohnaka K., Sakai Y., Nakao R., Yanase T., Haji M., Inagami T., Furuta H., Gou D. F., Nakamuta M. Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor. Biochem Biophys Res Commun. 1992 Mar 16;183(2):910–916. doi: 10.1016/0006-291x(92)90570-b. [DOI] [PubMed] [Google Scholar]
- Tiret L., Bonnardeaux A., Poirier O., Ricard S., Marques-Vidal P., Evans A., Arveiler D., Luc G., Kee F., Ducimetière P. Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction. Lancet. 1994 Oct 1;344(8927):910–913. doi: 10.1016/s0140-6736(94)92268-3. [DOI] [PubMed] [Google Scholar]
- Tiret L., Rigat B., Visvikis S., Breda C., Corvol P., Cambien F., Soubrier F. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992 Jul;51(1):197–205. [PMC free article] [PubMed] [Google Scholar]
