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Previous Volume 347:1916-1923 December 12, 2002 Number 24 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Peters, R. J.G. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Although epidemiologic studies have suggested that several genetic variants increase the risk of myocardial infarction, large-scale association studies that examine many polymorphisms simultaneously are required to allow reliable prediction of the genetic risk of myocardial infarction.

Methods We used a fluorescence- or colorimetry-based allele-specific DNA-primer–probe assay system to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction (2003 men and 816 women) and 2242 unrelated Japanese controls (1306 men and 936 women).

Results In an initial screening of the 112 polymorphisms for an association with myocardial infarction in 909 subjects, 19 polymorphisms were selected in men and 18 in women by means of logistic-regression analysis, after adjustment for age, body-mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. In a large-scale study involving the selected polymorphisms and the remaining 4152 subjects, similar logistic-regression analysis revealed that the risk of myocardial infarction was significantly associated with the C1019T polymorphism in the connexin 37 gene (P<0.001) in men and the 4G–668/5G polymorphism in the plasminogen-activator inhibitor type 1 gene (P<0.001) and the 5A–1171/6A polymorphism in the stromelysin-1 gene (P<0.001) in women.

Conclusions Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.

Source Information

From the Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake (Y.Y., M.T.); the Cardiovascular Division, Department of Pathophysiology, Nagoya University Graduate School of Medicine, Nagoya (H. Izawa, S.I., M.Y.); the Division of Cardiology, Kosei Hospital, Anjo (F.T.); the Division of Cardiology, Okazaki City Hospital, Okazaki (H. Ishihara); the Cardiovascular Center, Nagoya Daini Red Cross Hospital, Nagoya (H.H.); and the Department of Cardiology, Ogaki Municipal Hospital, Ogaki (T.S.) — all in Japan.

Address reprint requests to Dr. Yokota at the Department of Clinical Laboratory Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan, or at myokota{at}med.nagoya-u.ac.jp.

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Risk of Myocardial Infarction and Polymorphisms in Candidate Genes
Mannucci P. M., Peyvandi F., Ardissino D., Yamada Y., Yokota M.
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N Engl J Med 2003; 348:1176-1177, Mar 20, 2003. Correspondence

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