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Am J Physiol Heart Circ Physiol (April 4, 2002). doi:10.1152/ajpheart.00653.2001
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Articles in PresS, published online ahead of print April 4, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00653.2001
Submitted on July 25, 2001
Accepted on March 29, 2002

EcNOS gene polymorphism is associated with endothelium-dependent vasodilation in type 2 diabetes

Miyoko Komatsu1, Takahiko Kawagishi1*, Masanori Emoto1, Tetsuo Shoji1, Atsuko Yamada1, Kyoko Sato1, Masayuki Hosoi1, and Yoshiki Nishizawa1

1 Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

* To whom correspondence should be addressed. E-mail: takahiko{at}med.osaka-cu.ac.jp.

The association between ecNOS gene polymorphism and vascular endothelial function has not been clarified. We investigated the impact of ecNOS gene polymorphism on endothelial function in 95 type 2 diabetes (ecNOS genotype: 4b/b, n = 62; 4b/a, n = 30; 4a/a, n = 3). Flow-mediated (endothelium-dependent, FMD) and nitroglycerin-induced (endothelium-independent, NTG) vasodilations of the right brachial artery were studied using a phase-locked echo-tracking system. There were no significant differences in clinical characteristics among the ecNOS genotypes. The FMD was significantly lower in the patients with ecNOS4a allele than in those without ecNOS4a allele (P < 0.05). Multiple regression analysis showed that ecNOS4a allele and mean blood pressure were significant independent determinants for reduced FMD in all patients (R2 = 0.122, P = 0.0025). The ecNOS4a allele was an independent determinant for reduced FMD in smokers but not in nonsmokers. These results suggested that ecNOS4a allele is a genetic risk factor for endothelial dysfunction in diabetic patients, especially in smokers.




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