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Am J Physiol Heart Circ Physiol 283: H557-H561, 2002. First published April 4, 2002; doi:10.1152/ajpheart.00653.2001
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Vol. 283, Issue 2, H557-H561, August 2002

ecNOS gene polymorphism is associated with endothelium-dependent vasodilation in Type 2 diabetes

Miyoko Komatsu, Takahiko Kawagishi, Masanori Emoto, Tetsuo Shoji, Atsuko Yamada, Kyoko Sato, Masayuki Hosoi, and Yoshiki Nishizawa

Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan

The association between endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and vascular endothelial function has not been clarified. We investigated the impact of ecNOS gene polymorphism on endothelial function in 95 patients with 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 echotracking 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 suggest that ecNOS4a allele is a genetic risk factor for endothelial dysfunction in diabetic patients, especially in smokers.

endothelial constitutive nitric oxide synthase gene; diabetes mellitus; flow-mediated vasodilation; smoking


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