Association of endothelial nitric oxide synthase polymorphisms and haplotypes with ischemic stroke in Korean individuals with or without diabetes mellitus

Abstract

Abstract. 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.

Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke

“…[34][35][36][37] Lower nitric oxide plasma level was detected among 4a allele carriers than in the 4b wild-type allele. 31 A similar trend found in genotype-phenotype studies on NOS protein concentration and enzyme activity, indicates that protein expression and enzyme activity were lower in 4a4b genotype as compared to 4b4b genotype. 38 Moreover, the mutant 4a allele of eNOS may predispose a harmful effect on atherosclerosis, which is an independent risk factor for ischemic stroke.…”

“…These findings are in agreement with several case-control studies. [10][11][12]31,32 Akhter et al 33 reported that lower levels of nitric oxide is associated with ischemic stroke, indicating that eNOS has a neuroprotective effect and play the role of endothelial dysfunction in ischemic stroke pathogenesis. Recently, meta-analyses have reported the significant association between eNOS 4a/b polymorphism and increased risk of ischemic stroke, particularly in Asian population rather than Caucasian population.…”

Endothelial NO Synthase Gene Polymorphisms and Risk of Ischemic Stroke in Asian Population: A Meta-Analysis

“…For this reason, in T-786C polymorphism, two articles [29], [30] for recessive model were not sufficient to calculated pooled OR. After excluding articles for OR>3.0 [32], [41], [42], there were only two studies left sufficient to calculated pooled OR for recessive model, so we did not further investigate the association in recessive model.…”

Relationship between endothelial nitric oxide synthase gene polymorphisms and ischemic stroke: a meta-analysis

“…Data from 33 articles on the association between any of the three polymorphisms and ischemic stroke met the inclusion and exclusion criteria, and they were included in the meta‐analysis. There are 13 articles written in Chinese and 20 articles written in English. The final sample size was as follows: 5261 cases and 5823 controls for the G894T polymorphism, 4295 cases and 4682 controls for the 4b/a polymorphism, and 2698 cases and 3254 controls for the T786C polymorphism.…”

“…Data were extracted separately for these two ethnicities. Thus, 34 data sets were obtained: 25 data sets (24 articles) dealt with G894T , 18 with 4b/a , and 11 with T786C . One article that investigated 4b/a, and three articles that investigated T786C also investigated G894T.…”