Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been implicated in various diseases associated with cardiovascular risk factors, but little is known regarding the risks of ischemic stroke (IS) in patients with diabetes mellitus (DM). In this study, we evaluated the genotypes and haplotypes of three eNOS polymorphisms (-786T>C, 4a4b and 894G>T) in a Korean population of 223 IS patients and 206 controls classified into four groups: healthy subjects, type 2 DM patients without IS, IS patients without type 2 DM and IS patients with type 2 DM. The genotype frequency of 4a4b in the controls with type 2 DM differed significantly from that in the controls without DM (4b4b vs. 4a4b; OR=2.769; 95% CI 1.233-6.220) and the frequency of the -786C-4a-894G haplotype was higher in the controls with DM compared to the controls without DM (P=0.040). Additionally, the -786C-4b-894G haplotype was more common in the cases with DM than in the controls without type 2 DM (P=0.034). Our findings suggest that the eNOS 4a allele-associated genotype and haplotype is a risk factor for type 2 DM, and that the -786C-4b-894G haplotype is a risk factor for IS with DM.

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