Accumulation of Gene Polymorphisms Related to Plaque Disruption and Thrombosis Is Associated With Cerebral Infarction in Subjects With Type 2 Diabetes
- Naoto Katakami, MD, PHD1,
- Mitsuyoshi Takahara, MD, PHD1,
- Hideaki Kaneto, MD, PHD1,
- Ikki Shimizu, MD, PHD2,
- Keizo Ohno, MD, PHD3,
- Fukashi Ishibashi, MD, PHD4,
- Takeshi Osonoi, MD, PHD5,
- Atsunori Kashiwagi, MD, PHD6,
- Ryuzo Kawamori, MD, PHD7,
- Iichiro Shimomura, MD, PHD1,
- Munehide Matsuhisa, MD, PHD1 and
- Yoshimitsu Yamasaki, MD, PHD8
- 1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;
- 2Ehime Prefectural Central Hospital, Osaka, Japan;
- 3Ehime Prefectural Imabari Hospital, Osaka, Japan;
- 4Ishibashi Clinic, Osaka, Japan;
- 5Naka Kinen Clinic, Osaka, Japan;
- 6Department of Medicine, Shiga, University of Medical Science, Shiga, Japan;
- 7Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Juntendo, Japan;
- 8Center for Advanced Science and Innovation, Osaka University, Osaka, Japan.
- Corresponding author: Naoto Katakami, katakami{at}medone.med.osaka-u.ac.jp.
Abstract
OBJECTIVE It is believed that disruption of vulnerable atherosclerotic plaque and subsequent thrombus formation play critical roles in the pathogenesis of cerebral infarction. We simultaneously determined four relatively common genetic variants related to plaque rupture or subsequent local thrombus formation and evaluated the combined effect on cerebral infarction.
RESEARCH DESIGN AND METHODS We enrolled 3,094 Japanese type 2 diabetic subjects (62.7% male; aged 61.5 ± 8.4 years) and determined their genotypes regarding matrix metalloproteinase 9 C-1562T, coagulation factor XII (F12) C46T, von Willebrand factor (VWF) G-1051A, and plasminogen activator inhibitor (PAI-1) 675 4G/5G polymorphisms. The diagnosis of cerebral infarction was performed based on history, physical examination, and neuroimaging.
RESULTS The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of cerebral infarction. Interestingly, the prevalence of cerebral infarction was higher with the increase of the total number of four concomitant unfavorable proatherothrombotic alleles in each subject (P value for linear trend = 0.004). Furthermore, a multiple logistic regression analysis showed that the number of proatherothrombotic alleles was a risk factor for cerebral infarction independently of conventional risk factors (odds ratio for one-point increase in the number of proatherothrombotic allele 1.15 [95% CI 1.05–1.26], P = 0.004).
CONCLUSIONS Accumulation of gene polymorphisms related to plaque rupture and thrombus formation is likely associated with the prevalence of cerebral infarction in type 2 diabetic patients, suggesting that the combined information about these variants is useful to assess the risk of cerebral infarction.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received August 14, 2009.
- Accepted November 13, 2009.
- © 2010 by the American Diabetes Association.
