Polymorphism of Nitric Oxide Synthase Gene and Nitric Oxide Production in Serum in Cerebral Infarction / 中国康复理论与实践

@#Objective To observe the polymorphism of nitric oxide synthase(NOS)gene and the changes of nitric oxide(NO)in cerebral infarct.Methods The prospective case-control study was employed.Cases contained 193 subjects with cerebral infarction of internal carotid artery system within 2 weeks.Controls contained 103 subjects which came from the normal health checkup.The polymorphism in intron 4 of endothelial nitric oxide synthase(eNOS)gene were detected.NO content was measured by Griess diazotization assay and NOS activity by enzynatic assay.Results There were 48 subjects with allele a in intron 4 of eNOS gene(eNOS4a)in cases and 12 in controls.The frequencies of eNOS4a in cases was higher than that in controls(χ2=8.86,P=0.003).Multivariate Logistic regression analysis confirmed that eNOS4a was an independent risk factors for cerebral infarction(P=0.032).NO production and NOS activity were 6.04(3.83～11.49)μmol/L,(2.97±1.47)U/ml,respectively in cases,and 6.89(4.64～12.43)μmol/L,(3.16±1.46)U/ml,respectively in controls.NO production in cases were significantly lower than that in controls(P=0.022).There was not differential in NOS activity between these two groups(P=0.517).NO production and NOS activity were 5.07(3.18～7.62)μmol/L,(2.77±1.13)U/ml,respectively in the subjects with eNOS4a,and 6.89(4.64～12.43)μmol/L,(3.12±1.54))U/ml,respectively in the subjects without eNOS4a.NO production in the subjects with eNOS4a were significantly lower than that in the subjects without eNOS4a(P=0.001).The NOS activities were not significantly different in subjects with or without eNOS4a(P=0.100).Conclusion eNOS4a possibly exerted some effects on cerebral infarction by diminishing NO.

eNOS gene polymorphism in patients with acute coronary syndrome or variant angina in Korean / 대한내과학회지

BACKGROUND: Nitric oxide, also known as endothelial derived relaxing factor(EDRF), regulates the vascular tone and inhibits the proliferation of vascular smooth muscle cells and platelet adhesions and endothelium-leukocyte interactions. Thus, nitric oxide may be involved in the pathogenesis of atherosclerosis and vasospasm. We analyzed the genotype distributions of two eNOS gene polymorphisms in normal healthy Koreans and compared it with those in the patients with acute coronary syndrome and variant angina. METHODS: We analyzed the two eNOS polymorphisms (eNOS A/B polymorphism is the variable numbers of tandem repeat in intron 4 and eNOS T/G polymorphism is a mis-sense mutation in exon 7) using PCR and clinical characteristics of the risk factors for coronary artery disease in 142 normal healthy Koreans and 164 patients with acute coronary syndrome and 104 patients with variant angina. RESULTS: The genotype distribution of A/B polymorphism of eNOS gene, A/A, A/B, B/B was 4.9%, 21.1%, 74% in control group and 2.4%, 12.8%, 84.8% in the patients with acute coronary syndrome(p=0.02) and 2.9%, 16.3%, 80.8% in the patients with variant angina(p=NS), respectively. The genotype distribution of T/G polymorphism of eNOS gene, T/T, T/G, G/G was 1.4%, 15.5%, 83.1% in control group and 0.6%, 21.3%, 78.1% in the patients with acute coronary syndrome(p=NS) and 0%, 18.3%,81.7% in the patients with variant angina(p=NS), respectively. The odds ratio for acute coronary syndrome of non B/B(A/A & A/B) to B/B was 0.489 (95% CI : 0.257-0.928). We found that age, sex (male), diabetes mellitus, hyperlipidemia, smoking, B/B genotype were independent risk factors for acute coronary syndrome. But, in variant angina, smoking was the only significant independent risk factor(odds ratio=5.934, 95% CI 2.843-12.388, p< 0.05). CONCLUSION: The B/B genotype frequency of eNOS gene was significantly higher in patients with acute coronary syndrome than in normal controls. But neither A/B nor T/G polymorphism of eNOS gene was associated with variant angina. These results suggest that eNOS gene may play some roles in the pathogenesis of ACS rather than vasospasm.

Significance of eNOS Gene Polymorphism for the Prediction of Restenosis after Coronary Angioplasty in Patients with Ischemic Heart Disease

BACKGROUND: The restenosis after coronary angioplasty is the unresolved problem even if the improvement of interventional skills and pharmacological therapies. Nitric oxide, known as endothelial derived relaxing factor (EDRF), regulates the vascular tone and inhibits the proliferation of vascular smooth muscle cells and platelet adhesions and endothelium-leukocyte interactions. Nitric oxide is produced by endothelial nitric oxide synthase (eNOS). We studied the significance of eNOS gene polymorphism for the prediction of restenosis after coronary angioplasty in Koreans with ischemic heart disease. METHODS: We analyzed the two eNOS poly-morphisms using PCR (eNOS A/B polymorphism is the VNTR in intron 4 and eNOS T/G polymorphism is a missense mutation in exon 7) in 199 Korean patients who had 257 lesions undergoing percutaneous coronary angioplasty (ballooning=152, stenting=105). The angiography was repeated 6 months later to assess the relation between the rate of restenosis and types of eNOS gene polymorphism. RESULTS: We found no significant differences of restenosis rate in eNOS A/B and T/G polymorphism in those with balloon angioplasty or with stent (restenosis rate of A/A, A/B, B/B, respectively (n=257): 25% (1/4), 26% (14/53), 31% (62/200) (p=not significant), and T/T, T/G, G/G (n=249): 0% (0/3), 36% (16/44), 29% (58/202)(p=not significant)) Patients with A allele (non BB) or GG phenotype had lower restenosis rate, so we analyzed protective effect of non BB and GG phenotype on restenosis, but there was no significant statistical difference (restenosis rate of non BB and GG, BB and non GG respectively: 20% (15/57), 34% (16/47)(p=not significant)). CONCLUSION: eNOS A/B and T/G polymorphism is not associated with a significantly elevated risk of restenosis after coronary angioplasty.

Correlative study between polymorphism in ecNOS gene and ischemic stroke / 临床神经病学杂志

Objective To detect the relationship between ecNOS gene polymorphism and ischemic stroke in Dalian,China.Methods The polymorphism of intron 4 of ecNOS gene was analyzed in normal group(90 cases) and ischemic stroke group(170 cases) by a combination of polymerase chain reaction(PCR).Results In ischemic stroke group,hypertension, diabete mellitus, smoking, fibrinogen and internal carotid artery narrow were significantly different from those of control group(all P

A study of the association between polymorphism of endothelial nitric oxide synthase gene and diabetic nephropathy / 中国糖尿病杂志

Objective To investigate the association between a 894 G→T mutation at exon 7 of eNOS gene and diabetic nephropathy in type 2 diabetes mellitus of northern chinese Methods A case control study for 228 chinese subjects (including 143 type 2 diabetes mellitus with or without nephropathy and 85 normal control)was performed The number of the 894 G→T mutation alleles were determined by polymerase chain reaction and restriction fragment length polymorphism(PCR RFLP) method combined by DNA sequencing Results The frequency of the T allele and TG genotype at exon 7 were significantly higher in DN+ group than in DN group and control subjects(P