Abstract 2398: Polymorphisms of Angiotensin Converting Enzyme and Endothelial Nitric Oxide Synthase Genes Act Synergistically to Increase the Risk of Cardiovascular Events in Patients with Hypertrophic Cardiomyopathy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Akiyoshi Ogimoto ◽  
Hideki Okayama ◽  
Tomoaki Ohtsuka ◽  
Jun Suzuki ◽  
Katsuji Inoue ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hypertrophic Cardiomyopathy ◽  
Endothelial Nitric Oxide Synthase ◽  
Odds Ratio ◽  
Cardiovascular Events ◽  
Enos Gene ◽  
Converting Enzyme ◽  
History Of ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background: Patients with hypertrophic cardiomyopathy (HCM) have a small left ventricular cavity size due to hypertrophy. Therefore, reduction of venous return and intravascular volume in patients with HCM leads to low cardiac output and hypotension. We reported that the angiotensin converting enzyme insertion/insertion (ACE I/I) genotype, which leads to inhibitory renin-angiotensin system, is a significant risk factor for cardiovascular events (CE) in patients with HCM. Recently, the endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298Asp), which plays an important role in the modulation of cardiovascular physiology, is reported to be associated with heart diseases. Methods and Results: Genotyping at these loci was performed in 150 patients with HCM. This study design was a nested case-control study. The cardiovascular events were defined as cardiac death and hospitalization for stroke or congestive heart failure. Patients were divided into two groups: group A of 44 patients (29%) with one or more history of the cardiovascular events and group B of 106 patients (71%) without history of the cardiovascular events. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of CE. The odds ratio for cardiovascular events among persons who had ACE I/I genotype as compared with those with the other ACE genotypes was 2.5 (P < 0.01). In a dominant Asp allele model of the eNOS gene polymorphism, there was a significant difference in genotypes between the two groups (p < 0.01). In addition, there was a marked increase in the risk of CE among persons who were homozygous for both genotypes (ACE I/I and eNOS 298Glu/Glu) (odds ratio, 2.7, P < 0.01). Conclusion: The ACE I/I and eNOS 298Glu/Glu act synergistically to increase the risk of CE in patients with HCM. Genotyping at these two loci may be a useful approach for identification of persons with HCM at risk for CE.

scholarly journals Endothelial Nitric Oxide Synthase Gene Polymorphisms and Risk of Coronary Artery Disease

2003 ◽  
Vol 49 (3) ◽  
pp. 389-395 ◽  
Author(s):  
Maria Giovanna Colombo ◽  
Umberto Paradossi ◽  
Maria Grazia Andreassi ◽  
Nicoletta Botto ◽  
Samantha Manfredi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Odds Ratio ◽  
Enos Gene ◽  
Italian Population ◽  
Artery Disease ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract Background: Endothelial nitric oxide synthase (eNOS) could be a candidate gene for coronary artery disease (CAD). This study investigated the relationship of the eNOS Glu298→Asp and T786→C polymorphisms with the presence and severity of CAD in the Italian population. Methods: We enrolled 415 unrelated individuals who underwent coronary angiography. The severity of CAD was expressed by means of the Duke score. The eNOS Glu298→Asp and T786→C variants were analyzed by PCR. Results: There was significant linkage disequilibrium between the two eNOS polymorphisms (P &lt;0.0001). Both variants were significantly associated with the occurrence and severity of CAD (P = 0.01 and 0.004 for Glu298→Asp and T786→C, respectively). The risk of CAD was increased among individuals homozygous for the C allele of the T786→C polymorphism compared with individuals homozygous for the T allele (odds ratio = 2.5; P &lt;0.01) and was independent of the other common risk factors (P = 0.04). Moreover, individuals with both the Asp/Asp genotype of the Glu298→Asp polymorphism and at least one C allele of the T786→C variant in the promoter region of the eNOS gene had an increased risk of CAD (odds ratio = 4.0; P &lt;0.001) and a significantly higher mean Duke score (26.2 ± 2.9 vs 45.2 ± 3.7; P = 0.002) compared with individuals with the TT genotype and the Glu allele. Conclusions: The present study provides evidence that the Glu298→Asp and T786→C polymorphisms of the eNOS gene are associated with the presence and severity of angiographically defined CAD in the Italian population and that those individuals carrying both eNOS variants simultaneously might have a higher risk of developing CAD.

The Influence Of Endothelial Nitric Oxide Synthase (Enos) Genetic Polymorphisms On Cholesterol Blood Levels Among Type 2 Diabetic Patients On Atorvastatin Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Sarah Abdullah ◽  
Yazun Jarrar ◽  
Hussam Alhawari ◽  
Eyada Abed ◽  
Malek Zihlif
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lipid Profile ◽  
Genetic Polymorphisms ◽  
Endothelial Nitric Oxide Synthase ◽  
Diabetic Patients ◽  
Enos Gene ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background: Endothelial nitric oxide synthase (eNOS) plays a major role in the response of antihypercholesterol statin drugs. Genetic polymorphisms in the eNOS gene affect the activity of eNOS and thereby modulate statin response. Objectives: This study investigated the influence of major functional eNOS gene polymorphisms (rs2070744, rs1799983, and rs61722009) on the lipid profile of type 2 diabetes mellitus (T2DM) Jordanian patients treated with atorvastatin. Methods: The sample comprised 103 T2DM patients who attended the diabetes clinic of Jordan University Hospital. The T2DM patients had regularly been taking 20 mg atorvastatin. The atorvastatin response was calculated by measuring the lipid profile before and after three months of atorvastatin treatment. The eNOS genotypes of the subjects were analyzed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) assay. Results: No significant association was found between eNOS genetic polymorphisms and the response to atorvastatin (ANOVA, p > 0.05). In addition, no significant difference in the frequency of eNOS genotypes was found between T2DM patients and healthy subjects. However, patients with eNOS rs1799983, 4a/4a, and rs61722009 G/G genotypes showed a significantly lower levels of baseline total cholesterol (TC) and low density lipoprotein (LDL) than did patients carrying the rs1799983 4b/4b or rs61722009 T/T genotype (p < 0.05). The eNOS rs1799983 and rs61722009 polymorphisms were in complete linkage disequilibrium (D' = 1). Conclusion: Although no association was found between eNOS genetic polymorphisms and atorvastatin response, there was a significant association between the rs1799983 and rs61722009 genotypes and baselines levels of TC and LDL in Jordanian T2DM patients. These genetic variants affect cholesterol levels and may play a role in the susceptibility to cardiovascular diseases in T2DM patients. Further studies are needed to validate these findings.

scholarly journals Hyperhomocysteinemia, Endothelial Nitric Oxide Synthase Polymorphism, and Risk of Coronary Artery Disease

2006 ◽  
Vol 52 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Mohsen Kerkeni ◽  
Faouzi Addad ◽  
Maryline Chauffert ◽  
Anne Myara ◽  
Mohamed Ben Farhat ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Tunisian Population ◽  
Enos Gene ◽  
Artery Disease ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
G894t Polymorphism

Abstract Background: Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population. Methods: We used PCR with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay. Results: The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity. Conclusion: The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.

scholarly journals Analysis of Human Bradykinin Receptor Gene and Endothelial Nitric Oxide Synthase Gene Polymorphisms in End-Stage Renal Disease Among Malaysians

2014 ◽  
Vol 17 (1) ◽  
pp. 37-40 ◽  
Author(s):  
Vasudevan R. ◽  
Ismail P. ◽  
Jaafar N.I. ◽  
Mohamad N.A. ◽  
Etemad E. ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
End Stage Renal Disease ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Polymorphisms ◽  
Receptor Gene ◽  
Enos Gene ◽  
Stage Renal Disease ◽  
End Stage ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract The aim of this study was to determine the association of the c.894G>T; p.Glu298Asp polymorphism and the variable number tandem repeat (VNTR) polymorphism of the endothelial nitric oxide synthase (eNOS) gene and c.181C>T polymorphism of the bradykinin type 2 receptor gene (B2R) in Malaysian end-stage renal disease (ESRD) subjects. A total of 150 ESRD patients were recruited from the National Kidney Foundation’s (NKF)dialysis centers in Malaysia and compared with 150 normal healthy individuals. Genomic DNA was extracted from buccal cells of all the subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was carried out to amplify the products and the restricted fragments were separated by agarose gel electrophoresis. Statistical analyses were carried out using software where a level of p <0.05 was considered to be statistically significant. The genotypic and allelic frequencies of the B2R gene (c.181C>T, 4b/a) and eNOS gene (c.894G>T) polymorphisms were not statistically significant (p >0.05) when compared to the control subjects. The B2R and eNOS gene polymorphisms may not be considered as genetic susceptibility markers for Malaysian ESRD subjects.

scholarly journals Endothelial Nitric Oxide Synthase Gene Single-Nucleotide Polymorphism Predicts Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

2008 ◽  
Vol 28 (6) ◽  
pp. 1204-1211 ◽  
Author(s):  
Robert M Starke ◽  
Grace H Kim ◽  
Ricardo J Komotar ◽  
Zachary L Hickman ◽  
Eric M Black ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Subarachnoid Hemorrhage ◽  
Nitric Oxide Synthase ◽  
Cerebral Vasospasm ◽  
Endothelial Nitric Oxide Synthase ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Enos Gene ◽  
Single Nucleotide ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.

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