European Heart Journal Advance Access originally published online on July 28, 2006
European Heart Journal 2006 27(17):2081-2087; doi:10.1093/eurheartj/ehl177
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Association of Gln222Arg polymorphism in the deoxyribonuclease I (DNase I) gene with myocardial infarction in Japanese patients
1 Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
2 Division of Cardiology, Gunma Prefecture Cardiovascular Center, Gunma, Japan
3 Division of Cardiology, Maiduru Kyosai Hospital, Kyoto, Japan
4 Department of Legal Medicine, Gunma University Graduate School of Medicine, Gunma, Japan
5 Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Matsuoka, Fukui 910-1193, Japan
Received 16 December 2005; revised 6 June 2006; accepted 29 June 2006; online publish-ahead-of-print 28 July 2006.
* Corresponding author. Tel: +81 776 61 8287; fax: +81 776 61 8149. E-mail address: tyasuda{at}fmsrsa.fukui-med.ac.jp
See page 2031 for the editorial comment on this article (doi:10.1093/eurheartj/ehl157)
Aims We have recently reported that serum deoxyribonuclease I (DNase I) activity, which may be involved in apoptosis, increases abruptly in the early phase of acute myocardial infarction (MI) [Kawai Y, Yoshida M, Arakawa K, Kumamoto T, Morikawa N, Masamura K, Tada H, Ito S, Hoshizaki H, Oshima S, Taniguchi K, Terasawa H, Miyamori I, Kishi K, Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation 2004;109:2398–2400]. Death of vascular smooth muscle cells, in part because of apoptosis, is postulated to heighten susceptibility to disruption of vulnerable plaque, resulting in onset of MI. The present study evaluated the possibility that Gln222Arg polymorphism of the DNase I gene may be one of the factors involved in predisposition to MI.
Methods and results We assessed 611 Japanese patients: 311 with MI and 300 with stable angina pectoris (AP). Three common phenotypes determined by two common codominant alleles, DNASE1*1 and *2, whose corresponding gene products exhibit different properties, were found in these patient groups. The prevalence of DNASE1*2 was significantly higher in patients with MI than in those with AP (0.543 vs. 0.428, P<0.001), being confirmed by phenotyping of the second study population. Multiple logistic regression analysis showed that the odds ratio of DNASE1*2 was 1.51 [95% confidence interval (CI) 1.04–2.18]. The association of the DNASE1*2 allele with MI was statistically significant, being independent of other conventional risk factors.
Conclusion Our data demonstrate that Gln222Arg polymorphism in the DNase I gene is associated with MI in the Japanese patients.
Key Words: Myocardial infarction • Deoxyribonuclease I • Polymorphism • Genetics
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