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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

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