This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirashiki, A. Articles by Yokota, M. Search for Related Content PubMed PubMed Citation Articles by Hirashiki, A. Articles by Yokota, M.

CLINICAL RESEARCH: GENE POLYMORPHISMS AND CAD

Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors

Akihiro Hirashiki, MD^*, Yoshiji Yamada, MD, PhD^,*, Yosuke Murase, MD^*, Yoriyasu Suzuki, MD^*, Hiroki Kataoka, MD^*, Yasutsugu Morimoto, MD^*, Toru Tajika, MD^*, Toyoaki Murohara, MD, PhD and Mitsuhiro Yokota, MD, PhD, FACC

^* Division of Cardiology, Okazaki City Hospital, Okazaki, Japan
Department of Gene Therapy, Gifu International Institute of Biotechnology, Kakamigahara, Japan
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Department of Clinical Pathophysiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Manuscript received April 6, 2003; revised manuscript received May 30, 2003, accepted June 16, 2003.

^* Reprint requests and correspondence: Dr. Yoshiji Yamada, FAHA, Department of Gene Therapy, Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan.
yoyamada{at}giib.or.jp

OBJECTIVES: The aim of the study was to identify genes that confer susceptibility to coronary artery disease (CAD) in low- or high-risk men or women separately and thereby to assess the genetic risk of CAD in such individuals.

BACKGROUND: The prevention of CAD would be facilitated by the identification of genes that confer susceptibility to this condition independently in low- or high-risk individuals, as defined by conventional risk factors.

METHODS: The study population comprised 1,661 unrelated Japanese individuals, including 1,011 patients with CAD and 650 control subjects. Among all study subjects, 601 individuals (high-risk subjects) had hypertension, diabetes mellitus, and hypercholesterolemia, and 1,060 individuals (low-risk subjects) had none of these risk factors for CAD. The genotypes for 37 polymorphisms of 31 candidate genes were determined by a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system.

RESULTS: Multivariate logistic regression analysis, with adjustment for age, body mass index, and the prevalence of smoking and hyperuricemia, revealed that the –219GT polymorphism of the apolipoprotein E gene in low-risk men, the –1171/5A6A polymorphism of the stromelysin-1 gene in low-risk women, the 1019CT polymorphism of the connexin 37 gene in high-risk men, and the 3932TC polymorphism of the apolipoprotein E gene in high-risk women were significantly associated with CAD. A stepwise forward selection procedure revealed that the effects of these polymorphisms on CAD were statistically independent of age or conventional risk factors.

CONCLUSIONS: Genotyping of these polymorphisms may prove informative for assessment of the genetic risk of CAD in low- or high-risk men or women.

Abbreviations and Acronyms   BMI = body mass index   BP = blood pressure   CAD = coronary artery disease   HbA1c = glycosylated hemoglobin   LDL = low-density lipoprotein   MI = myocardial infarction   SNP = single nucleotide polymorphism

This article has been cited by other articles:

				W. Koch, P. Hoppmann, A. de Waha, A. Schomig, and A. Kastrati Polymorphisms in thrombospondin genes and myocardial infarction: a case-control study and a meta-analysis of available evidence Hum. Mol. Genet., April 15, 2008; 17(8): 1120 - 1126. [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]

				F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]

				L. Ho, V. Bos, and A. E. Kunst Differences in Cause-of-Death Patterns Between the Native Dutch and Persons of Indonesian Descent in the Netherlands Am J Public Health, September 1, 2007; 97(9): 1616 - 1618. [Abstract] [Full Text] [PDF]

				S. Abilleira, S. Bevan, and H. S Markus The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis J. Med. Genet., December 1, 2006; 43(12): 897 - 901. [Abstract] [Full Text] [PDF]

				J. P. Casas, G. L. Cavalleri, L. E. Bautista, L. Smeeth, S. E. Humphries, and A. D. Hingorani Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review Am. J. Epidemiol., November 15, 2006; 164(10): 921 - 935. [Abstract] [Full Text] [PDF]

				X. F. Figueroa, B. E. Isakson, and B. R. Duling Vascular Gap Junctions in Hypertension Hypertension, November 1, 2006; 48(5): 804 - 811. [Full Text] [PDF]

				G. P. Rossi, G. Maiolino, M. Zanchetta, D. Sticchi, L. Pedon, M. Cesari, D. Montemurro, R. De Toni, S. Zavattiero, and A. C. Pessina The T-786C Endothelial Nitric Oxide Synthase Genotype Predicts Cardiovascular Mortality in High-Risk Patients J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1166 - 1174. [Abstract] [Full Text] [PDF]

				P G Horan, A R Allen, C C Patterson, M S Spence, P G McGlinchey, and P P McKeown The connexin 37 gene polymorphism and coronary artery disease in Ireland. Heart, March 1, 2006; 92(3): 395 - 396. [Full Text] [PDF]

				S. Ye Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome Cardiovasc Res, February 15, 2006; 69(3): 636 - 645. [Abstract] [Full Text] [PDF]

				A. C. Newby and J. L. Johnson Genetic Strategies to Elucidate the Roles of Matrix Metalloproteinases in Atherosclerotic Plaque Growth and Stability Circ. Res., November 11, 2005; 97(10): 958 - 960. [Full Text] [PDF]

				G. D. Kolovou, K. K. Anagnostopoulou, K. D. Salpea, D. B. Panagiotakos, I. S. Hoursalas, M. A. Cariolou, K. Koniavitou, and D. V. Cokkinos Apolipoprotein E Genotype in Matched Men and Women with Coronary Heart Disease Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 391 - 396. [Abstract] [Full Text] [PDF]

				N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]

				W. Koch, J. Mehilli, A. Pfeufer, A. Schomig, and A. Kastrati Apolipoprotein E gene polymorphisms and thrombosis and restenosis after coronary artery stenting J. Lipid Res., December 1, 2004; 45(12): 2221 - 2226. [Abstract] [Full Text] [PDF]

				G. P. Rossi, G. Maiolino, J. P. Casas, A. D. Hingorani, S. E. Humphries, L. Smeeth, and L. E. Bautista Do Meta-Analyses of Association Studies of Endothelial Nitric Oxide Synthase Variants and Ischemic Heart Disease Provide Conclusive Answers? * Response Circulation, September 14, 2004; 110(11): e305 - e306. [Full Text] [PDF]

				D. E. Lanfear, S. Marsh, S. Cresci, W. D. Shannon, J. A. Spertus, and H. L. McLeod Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans J. Am. Coll. Cardiol., July 7, 2004; 44(1): 165 - 167. [Abstract] [Full Text] [PDF]

				G. P. Rossi and G. Maiolino Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors J. Am. Coll. Cardiol., July 7, 2004; 44(1): 209 - 209. [Full Text] [PDF]

				A. Hirashiki, Y. Yamada, and M. Yokota Reply J. Am. Coll. Cardiol., July 7, 2004; 44(1): 209 - 210. [Full Text] [PDF]