Association of Endothelial Nitric Oxide Synthase and Angiotensin-Converting Enzyme Genes Polymorphism With In-Sent Restenosis of Bare Metal Stents vs Drug-Eluting Stents in Egyptians.

Despite its unequivocal superiority compared with balloon angioplasty, coronary stenting did not abolish restenosis. We aimed to evaluate the associations between a common single nucleotide polymorphism occurring in endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) genes and the risk of in-stent restenosis (ISR) of bare metal stents vs drug-eluting stents (BMS vs DES) implanted in Egyptian patients. Two hundred patients who had coronary stenting were divided into group I (n = 98) who received a BMS and group II (n = 102) who received a DES. eNOS and ACE genes polymorphism were analyzed by polymerase chain reaction (PCR). We found that the GA and AA genotypes of the eNOS gene were associated with the ISR with both BMS and DES. However, the ACE gene was not associated with ISR. We concluded that eNOS gene polymorphism is associated with ISR. Hypertension, stent length, and AA genotype of the eNOS gene were found to be independent predictors of the occurrence of ISR after both BMS and DES use.

Relationship between the G894T polymorphism of endothelial nitric oxide synthase gene and lipid metabolism among hypertensive disorder complicating pregnancy patients / 解剖学报

Objective To investigate the relationship between the G894T polymorphism of the endothelial nitric oxide synthase (eNOS) gene and the lipid metabolism in patients with irypertensive disorder complicating pregnancy (HDCP). Methods The 528 cases of HDCP patients admitted to the Xingtai Third Hospital from January 2016 to January 2020 were selected as the research objects, and 128 normal pregnant women during the same period were selected as the control group. The fasting peripheral venous blood of all stud)' subjects in the early morning was collected, and blood lipid indexes, cystatin C (CysC) and uric acid levels and other biochemical index levels were measured. According to the blood lipid level, it was divided into normal blood lipid group and dyslipidemia group. The dyslipidemia group included 4 subgroups [ hyper triglyceride (TG) blood group (T G

Association of endothelial nitric oxide synthase gene variants with preeclampsia.

BACKGROUND: Preeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology. The endothelial nitric oxide synthase (eNOS) gene and nitric oxide (NO) levels has been reported to be associated with PE predisposition in various populations. Therefore, present study was designed to investigate the role of NO levels and eNOS gene variants in preeclamptic women in Pakistan. METHODS: A total of 600 women were evaluated, 188 of PE with mild features, 112 of PE with severe features and 300 normotensive pregnant women. NO levels were detected by Greiss reaction method and genotyping following sequencing was conducted for eNOS gene variants. Further insilico studies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation. RESULTS: Reduced concentrations of NO were reported in all PE groups (p < 0.05) as compared to controls. The frequency of c.894 T (p.298Asp) and g.-786C alleles were significantly associated with PE. In addition, novel homozygous variant g.2051G > A was also significantly associated with PE when compared to normotensive women. Dynamic simulation studies revealed that Glu298Asp mutation destabilize the protein molecule and decrease the overall stability of eNOS protein. Molecular docking analysis of mutant promoter with transcription factors STAT3 and STAT6 proposed changes in protein regulation upon these reported mutations in upstream region of the gene. CONCLUSION: Considering the results of current study, the functional alterations induced by these variants may influence the bioavailability of NO and represents a genetic risk factor for increased susceptibility to PE. However, large studies or meta-analysis are necessary to validate these findings.

Preeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology characterized by increased hypertension and proteinuria after 20 weeks of gestation. The present study was directed to determine the role of eNOS in susceptibility to PE and the association of c.894G > T (p.(Glu298Asp), intron 4b/4a, g.-786 T > C and other possible variants of eNOS gene with preeclampsia in Pakistani population. Computational analysis of identified variants in the coding and non-coding region of the eNOS gene was also conducted to determine the change in gene regulation and further protein stability. A total of 600 women were evaluated, 188 with mild and 112 with PE with severe features PE with 300 normotensive pregnant women. NO levels and genotyping following sequencing was conducted for eNOS gene variants. Further insilico studies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation. Data from the current study suggest that there might be other risk variants of the eNOS gene (g.2051G > A and g.1861G > A) and lower levels of serum NO that confers in an increased risk of PE. The detailed computational investigation further confirmed the deformities and changes in protein flexibility upon Glu298Asp. These structural alterations might be associated with preeclampsia. Variants in the promoter region of the eNOS gene further validate the change in gene regulation for the onset of disease. Identification of key structural and functional features in eNOS protein and gene regulatory region might be used for designing specific drugs for therapeutic purpose.

The Correlation of Endothelial Nitric Oxide Synthase (eNOS) Polymorphism and Other Risk Factors with Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study.

OBJECTIVE: Endothelial nitric oxide synthase gene (eNOS) polymorphism is an association with cerebral aneurysm formation, rupture, and vasospasm and plays a role in the a functional outcome. PATIENTS AND METHODS: The aim of the study was to evaluate the role of eNOS gene polymorphism and further assess the predictors of outcome in the aneurysmal subarachnoid hemorrhage (aSAH). A prospective case-control study was conducted from 2009 to 2012 among those who presented with aSAH. A serum sample was collected from aSAH patients along with age and sex-matched healthy controls. The frequency of polymorphism of eNOS gene and other factors (demographic and aneurysmal) were correlated with functional outcome at six month of follow-up. RESULTS: 100 patients with aSAH and 100 healthy controls were enrolled in the cohort. The mean age of the patient group was 51.61 years and control group was 45.81 years with a male:female ratio of 1:1.38 and 1:1.08 for patients and controls, respectively. Among all eNOS polymorphisms, 4BB (65%) 24-VNTR, TT (71%) of T-786C, and GG (71%) of G947T were the most common and frequency was similar in the control group. The occurrences of hypertension, smoking, diabetes were 32%, 37%, and 7% respectively in the patient group. Maximum patients were in WFNS grade 1 (53%) followed by 23% grade 2 and only 10% in grade 4. Fisher grade 3 (57%) was the most common followed by Fisher grade 4 (28%). Most aneurysms (97%) were in anterior circulation. 83% of the aneurysms were clipped and 10% underwent coiling. Size-wise most of the aneurysms were in the middle group (6-9 mm) followed by bigger group (>10 mm) (37%); only 6% aneurysms were in the small aneurysm (<6 mm) group. 33% of the patients had evidence of vasospasm. TT of G894T polymorphism (60%) had the highest incidence of vasospasm. Univariate analysis showed smoking (OR: 3.19, CI: 1.19-8.84, P = 0.01), 4AA (OR: 12.15, CI: 1.13-624.9, P = 0.03) variety of 24-VNTR polymorphism, CC (OR: 15.39, CI: 1.60-762.8, P = 0.01) variety of T786C polymorphism, Fisher grade 4 (OR: 3.43, CI: 1.24-9.68, P = 0.01), WFNS grade (poor vs. good) (OR: 3.42, CI: 1.17-10.12, P = 0.02), vasospasm (OR: 3.84, CI: 1.42-10.75, P = 0.006), intraoperative rupture (OR: 4.77, CI: 1.55-15.27, P = 0.004) were significantly related with unfavorable outcome at 6 months follow-up. In regression analysis, smoking (CI: 0.06-0.69, P = 0.01), Fisher grade 4 (CI: 0.09-1.00, P = 0.05), and intraoperative rupture (CI: 0.05-0.89, P = 0.03) were correlated with an unfavorable outcome at 6 months follow-up. CONCLUSION: The eNOS gene polymorphism, smoking, clinical grade (WFNS), Fisher grade, intraoperative rupture, and vasospasm play a role in functional outcome after the treatment of cerebral aneurysms.

Involvement of endothelial nitric oxide synthase gene variants in the aggressiveness of uterine cervical cancer.

To date, few studies explore the involvement of endothelial nitric oxide synthase (eNOS) gene variants in uterine cervical cancer. Therefore, we conducted this study to assess the clinical implication of eNOS in cervical carcinogenesis, clinicopathological characteristics and patient survival. One hundred and seventeen patients with cervical invasive cancer and 95 with preinvasive lesions and 330 control women were consecutively enrolled. Real time polymerase chain reaction was used to examine the genotypic distributions of eNOS single nucleotide polymorphisms (SNPs) rs1799983 (894G>T) at the exon 7 region and rs2070744 (-786T>C) at the promoter region. Our results indicated no significant associations among genotypic distributions of eNOS SNPs and patients with cervical invasive cancer and those with preinvasive lesions as well as normal controls. However, cervical cancer patients with genotypes TC/CC in eNOS SNP rs2070744 carried less risk of advanced stage [odds ratios (OR) = 0.30, 95% confidence interval (CI)=0.09-0.97, p=0.036], parametrium invasion (OR=0.16, 95% CI=0.02-0.75, p=0.009) and pelvic lymph node metastasis (OR=0.12, 95% CI=0.01-0.89, p=0.016). In conclusion, although eNOS SNPs rs2070744 and rs1799983 do not display significant associations with cervical carcinogenesis and patient survival, cervical cancer patients with genotypes TC/CC in rs2070744 carry less risk of advanced stage, parametrium invasion and pelvic lymph node metastasis in Taiwan.

DNA Methylation in Pediatric Obstructive Sleep Apnea: An Overview of Preliminary Findings.

Obstructive sleep apnea (OSA) is characterized by phenotypic variations, which can be partly attributed to specific gene polymorphisms. Recent studies have focused on the role of epigenetic mechanisms in order to permit a more precise perception about clinical phenotyping and targeted therapies. The aim of this review was to synthesize the current state of knowledge on the relation between DNA methylation patterns and the development of pediatric OSA, in light of the apparent limited literature in the field. We performed an electronic search in PubMed, EMBASE, and Google Scholar databases, including all types of articles written in English until January 2017. Literature was apparently scarce; only 2 studies on pediatric populations and 3 animal studies were identified. Forkhead Box P3 (FOXP3) DNA methylation levels were associated with inflammatory biomarkers and serum lipids. Hypermethylation of the core promoter region of endothelial Nitric Oxide Synthase (eNOS) gene in OSA children were related with decreased eNOS expression. Additionally, increased expression of genes encoding pro-oxidant enzymes and decreased expression of genes encoding anti-oxidant enzymes suggested that disturbances in oxygen homeostasis throughout neonatal period predetermined increased hypoxic sensing in adulthood. In conclusion, epigenetic modifications may be crucial in pediatric sleep disorders to enable in-depth understanding of genotype-phenotype interactions and lead to risk assessment. Epigenome-wide association studies are urgently needed to validate certain epigenetic alterations as reliable, novel biomarkers for the molecular prognosis and diagnosis of OSA patients with high risk of end-organ morbidity.

Associations of genetic variations of the endothelial nitric oxide synthase gene and environmental carcinogens with oral cancer susceptibility and development.

Oral cancer is a major head and neck cancer that is reported to be causally associated with genetic factors and environmental carcinogens. Endothelial nitric oxide synthase (eNOS) was reported to modulate carcinogenesis and progression through nitric oxide (NO) production. Genetic polymorphisms in the eNOS gene can regulate its transcription and further mediate NO production. The purpose of this study was to explore the influences of eNOS gene polymorphisms combined with environmental carcinogens on the predisposition for oral cancer. Two single-nucleotide polymorphisms (SNPs) of the eNOS gene, -786 T > C (rs2070744) and 894G > T (rs1799983), were genotyped in 1200 controls and 1044 patients with oral cancer using a TaqMan-based real-time polymerase chain reaction (PCR). We found that patients who carried the -786 T > C TC genotype were at higher risk for developing an advanced clinical stage (stage III/IV) compared to those with the -786 T > C TT genotype; however, there was no significant association of the two individual SNPs with oral cancer between patients and the control group. According to behavioral exposure to environmental carcinogens, the presence of these two eNOS SNPs combined with tobacco use and/or betel quid chewing profoundly enhanced the risk of oral cancer. Moreover, carriers with the betel quid-chewing habit who had haplotypes of the two eNOS SNPs more easily developed oral cancer. These results indicated an involvement of -786 T > C polymorphisms in the progression of oral cancer and support the interaction between eNOS gene polymorphisms and environmental carcinogens as a predisposing factor of oral carcinogenesis.

Endothelial nitric oxide synthase gene polymorphisms in patients with slow coronary flow.

BACKGROUND AND AIMS: The aim of this study was to explore potential associations of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow (SCF). The association between plasma nitrate and nitrite (NO x ) concentrations and eNOS gene polymorphisms was also assessed. MATERIALS AND METHODS: The intron 4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated DNA blood samples obtained from the SCF patient group (n = 30) and healthy group consisted of age- and sex-matched controls (n = 61). RESULTS: Plasma NO x level was significantly lower in patients with SCF than in controls. In addition, patients with SCF have significantly lower nitric oxide levels than control subjects within each genotype variants. The allele and genotyped frequencies of the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with SCF and the controls. Plasma NO x concentrations with respect to the relevant genotypes were found insignificant. DISCUSSION AND CONCLUSION: Plasma NO x is lower in patients with SCF than in healthy subjects. Our findings may suggest the lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS gene and SCF.

Promoter polymorphism T-786C, 894G→T at exon 7 of endothelial nitric oxide synthase gene are associated with risk of osteoporosis in Sichuan region male residents.

OBJECTIVE: To investigate the association between genetic polymorphism of T-786C in promoter region, 894G→T at exon 7 of endothelial nitric oxide synthase (eNOS) gene and osteoporosis (OP) disease. METHOD: The genotypes of 350 patients with osteoporosis and 350 healthy controls were detected by polymerase chain reaction (PCR) and DNA sequencing. The allele ratios and genotype distributions in the patients and controls were assessed using the Pearson χ(2)-test. Odds ratios (OR) with two tailed P-values and 95% confidence intervals (CI) were calculated as a measure of the association of the eNOS genotypes with OP. RESULT: the C allele distribution frequency of T-786C eNOS gene in OP group (8.5%) was significantly higher than that in control group (3.9%), relative risk (OR) of OP associated with the CC genotype was 2.68 (95% CI, 0.92 to 1.37). The T allele frequency of 894G→T at exon 7 in eNOS gene in OP group (11.5%) was also significantly higher than that in control group (5.2%), OR of OP associated with the TT genotype was 2.60 (all P<0.05). CONCLUSION: The analysis results indicated that both T-786C in promoter region and 894G→T at exon 7 of eNOS gene might be genetic predisposal factors of OP, these polymorphisms may be independently or synergic with other loci to have an impact on the incidence of OP.

Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia.

Preeclampsia (PE) is characterized by hypertension and proteinuria, occurring after the 20th week of pregnancy in women who have had no previous symptoms. The disease progresses with generalized vasoconstriction and endothelial dysfunction. Clinically, it is important to diagnose the severe form of the disease (sPE), in which blood pressure and proteinuria are much higher. Recently, the gestational age (GA) of the onset of PE has led to the classification of this disease as early (GA <34 weeks) and late (GA ≥34 weeks). Several genetic polymorphisms affecting endothelial nitric oxide synthase (eNOS) levels or function were described, including G894T (Glu298Asp), VNTR b/a (variable-number 27-bp tandem repeat) and T-786C (promoter) polymorphisms. Thus, the aim of this study was to compare the distribution of G894T, VNTR b/a and T-786C polymorphisms and their haplotypes in Brazilian early and late sPE, as well as in normotensive pregnant. A total of 201 women were evaluated, 53 with early sPE, 45 with late sPE and 103 as normotensive pregnant women. The frequency of 894T allele was higher in late sPE vs normotensive pregnant, and 894TT genotype was higher in late sPE vs early sPE and normotensive pregnant. For VNTR b/a polymorphism, higher frequencies of aa genotype and a allele were observed in early sPE vs late sPE and normotensive pregnant. Besides, the frequency of haplotype T-b-C was higher in late sPE vs early sPE and normotensive pregnant. Considering the results found for eNOS polymorphisms, it is possible to suggest that the functional alterations induced by these two polymorphisms may influence the time of severe PE onset, although both alterations are putatively associated with low NO bioavailability. However, other studies are necessary to validate these findings and clarify this issue.

Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene.

A case-control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% (P<0.01) lower. In the population, systolic/diastolic blood pressure increased over 7.6 years (median) by 9.7/6.8 mm Hg in 28 TT homozygotes and by 3.8/1.9 mm Hg in 2694 C allele carriers (P≤0.0004). The blood pressure rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6-11.1; P=0.028) and 4.8 mm Hg diastolic (CI, 1.5-8.2; P=0.0046) greater in TT homozygotes, with no differences between the CT and CC genotypes (P≥0.90). Among 2013 participants normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37; P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension.

Association of G894T polymorphism in endothelial nitric oxide synthase gene with the risk of ischemic stroke: A meta-analysis.

Findings of a previous meta-analysis demonstrated no association between G894T polymorphism in endothelial nitric oxide synthase (eNOS) gene and ischemic stroke. Results of other studies have also been inconsistent. Updated meta-analysis was performed to assess the association between the eNOS gene G894T (rs1799983) polymorphism and the risk of ischemic stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effects models were calculated. Heterogeneity in the studies was evaluated using the I2. Meta-regression and the 'leave-one-out' sensitive analysis were used to examine the potential sources of between-study heterogeneity. Publication bias was estimated using the Egger's test. Data were available for 6,607 cases and 6,947 controls from 22 studies. Studies deviating from the Hardy-Weinberg equilibrium (HWE) in the controls and the key contributors to between-study heterogeneity were excluded. Significant associations between eNOS gene G894T polymorphism and the risk of ischemic stroke were observed in the dominant (OR 1.249; 95% CI, 1.145-1.361), the recessive (OR 1.255; 95% CI, 1.082-1.456) and the codominant models (OR 1.195; 95% CI, 1.115-1.281). Moreover, in the subgroup analysis based on the region (Asia and Europe), significant associations were observed between the dominant and codominant genetic models but not in the recessive model. The results of our meta-analysis suggested that eNOS gene G894T polymorphism was associated with the increased risk of ischemic stroke, and that the T allele may be an important risk factor for ischemic stroke. However, further studies are required to confirm this result.

Association study of ACE and eNOS single nucleotide polymorphisms with Henoch-Schönlein purpura nephritis.

Previous studies have shown that insertion/deletion polymorphisms in the angiotensin-converting enzyme (ACE) gene and the endothelial nitric oxide synthase (eNOS) gene are associated with Henoch-Schönlein purpura nephritis (HSPN). However, further studies are required to prove the relationship between HSPN and ACE and eNOS single nucleotide polymorphisms (SNPs). We studied six ACE SNPs and two eNOS SNPs by genotyping HSPN patients. Statistical analyses indicate that four ACE SNPs and two eNOS SNPs are associated with HSPN susceptibility. A cumulative effect analysis suggested that an increased number of unfavourable genotypes may lead to an increased risk of HSPN. By comparing alleles, genotypes and haplotypes that are associated with lupus nephritis (LN) and HSPN, we found genetic heterogeneity between HSPN and LN.

Inhibition of TGF-ß1 by eNOS gene transfer provides cardiac protection after myocardial infarction.

OBJECTIVE: Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) have been implicated in protection against myocardial ischemia injury. This study was designed to explore a new method of therapy for myocardial injury by eNOS gene transfection. METHODS: A rat model of myocardial infarction (MI) was established by left anterior descending (LAD) coronary artery ligation. eNOS gene in an adenovirus vector was delivered locally into the rat heart and hemodynamic parameters were examined after 3 weeks, Matrix metalloproteinase-2 and 9 (MMP-2, MMP-9) mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR), and the protein levels of eNOS, caspase-3, and transforming grouth factor ß1 (TGF-ß1) were determined by western blot assay. RESULTS: eNOS gene transfer significantly reduced cardiomyocyte apoptosis and improved cardiac function. In addition, eNOS significantly reduced the mRNA levels of MMP-2 and MMP-9. In the eNOS gene transfected group, the activation of caspase-3 and TGF-ß1 were decreased. However, the protection was reversed by administration of the NOS inhibitor, N(ω)-nitro-l-arginine methyl ester (L-NAME). CONCLUSION: These results demonstrate that the eNOS provides cardiac protection after myocardial infarction injury through inhibition of cardiac apoptosis and collagen deposition, and suppression of TGF-ß1.

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.

The association between polymorphisims of aldose reductase gene and endothelial nitric oxide synthase and diabetic nephropathy / 医学研究生学报

Objective:To investigate the association between polymorphisims of both the 894G→T at exon 7 of endothelial nitric oxide synthase(eNOS) gene and the C-106T at promotor region of aldose reductase(AR) gene and type 2 diabetic nephropathy(DN) of Chinese. Methods: A case-control study for 202 Chinese subjects was performed.The genotypes and alleles of polymorphisims of 894G→T at exon 7 of eNOS gene and C-106T at promotor region of AR gene were determined by polymerase chain reaction restriction fragment lenth polymorphism method(PCR-RFLP). Results:The frequency of the T allele and TG genotype at exon 7 of eNOS gene and the T allele and CT genotype at promotor region of AR gene were significantly higher in DN+ group than that in DN-group and control group(P0.05).The type 2 diabetes with coexistence of the T allele/TG genotype of eNOS gene and T allele/CT genotype of AR gene had higher incidence of DN(P

Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction / 中国实用内科杂志

Objective To investigate the association of the Glu298-Asp(894G→T)mutation at exon 7 of the endothelial nitric oxide synthase gene and acute myocardial infarction.Methods By using the designed primers based on flanking sequences of the Glu298-Asp mutation at exon7 of eNOS, 894G→T fragments were amplified by nested PCR from genomic DNA of healthy control and AMI subjects, digested by restriction enzyme after amplification and detected by agarose gel electrophoresis for 894G→T genotyping. To count the genotype and allele frequencies, the significance of difference in the genotype and allele between two groups were assessed by statistical analysis.Results Three genotypes containing GG, GT, TT were identified on the 894 site of the eNOS gene exon 7 in both AMI and controls. In AMI group, there were 25 patients having 9 homozygotes, the other 16 having heterozygotes. In controls, there were 13 cases with G894T mutation,all having heterozygotes. The mutation frequency of TT homozygote allele has extraordinary significant difference between two groups (P

The association of a polymorphism in endothelial nitric oxide synthase gene with diabetic nephropathy / 中华检验医学杂志

Objective To examine the association of intron 4 polymorphism in endothelial nitric oxide synthase ( eNOS) gene with diabetic nephropathy and its distribution in different ethnic groups of Singapore. Methods 258 patients with diabetic duration longer than 10 years (150 Chinese, 71 Malay and 37 Indian) were selected from both inpatients and outpatients of National University Hospital. Polymorphism was identified by DNA extraction, PCR, Cloning and sequencing. Results All published studies identified that the 27bp repeat polymorphism in intron 4 was biallelic ( a and b alleles ). Our study found a third allele-allele c, with six 27bp repeats. It was also demonstrated that there was no significant difference in overall allele distribution among the three main ethnic groups and the intron 4 polymorphism didn't show any association with diabetic nephropathy. Conclusion The intron 4 polymorphism was triallelic. We failed to demonstrate any association between this polymorphism with diabetic nephropathy.

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.