Endothelial Nitric Oxide Synthase G894T Gene Polymorphism and Essential Hypertension in the Chinese Population: a Meta-Analysis Involving 11,248 Subjects

Abstract

Background The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism has been suggested to be linked to the risk of essential hypertension (EH), however the results are still debatable. Objective and Methods To assess the association between eNOS G894T gene polymorphism and EH, such electronic databases as Pubmed, Embase, Web of Science, China Biological Medicine Database (CBMD) and China National Knowledge Infrastructure (CNKI) were searched. The selection criteria were as follows: a) Evaluation of the association of eNOS G894T gene polymorphism and EH. b) EH diagnosis in compliance with EH diagnosis criteria of the World Health Organization (WHO) in 1999. c) The study results were in line with the Hardy-Weinberg equilibrium (HWE). In 23 separate studies with 11,248 subjects the relation between eNOS G894T gene polymorphism and EH was analyzed by current meta-analysis. Random effect model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). Results In this eNOS G894T gene polymorphism and EH meta-analysis in the Chinese population, the distribution of T allele frequency was 0.154 for EH group and 0.128 for the control group. A significant association was found between G894T gene polymorphism and EH (p=0.0007). The pooled OR for the distribution frequency of T allele was 1.33 (95% CI:1.13-1.56, Pheterogeneity <0.00001). In the stratified analysis by ethnicity, there was a significant association in Han subgroup (p=0.005). The pooled OR for the distribution frequency of T allele was 1.31 (95% CI:1.09-1.59, Pheterogeneity <0.00001). No significant increased risk for EH was found in the non-Han subgroup (p=0.08). Conclusion In the current meta-analysis, T allele of eNOS G894T gene was suggested to be related to the increased risk of EH in the Chinese population, particularly in those of Han ethnicity.

The Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism Increases Myocardial Infarction Risk: A Meta-Analysis

“…Genetic polymorphisms of the eNOS gene are good candidates for predicting the risk associated with cardiovascular diseases such as coronary artery disease, atrial fibrillation, and essential hypertension [ 26 – 28 ]. eNOS G894T is one of the most common variants of eNOS, the others being T-786C and 4b4a mutations.…”

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

“…eNOS-derived NO plays an important role in the maintenance of vascular homeostasis, including regulation of the cerebral circulation [10]. Besides, previous studies suggested that eNOS gene (4b/a,T-786C,G894T) polymorphisms are significantly associated with hypertension [47], [48], total cholesterol and low-density lipoprotein cholesterol levels [49], [50].…”

Impact on Longevity of Genetic Cardiovascular Risk and Lifestyle including Red Meat Consumption

“…This polymorphism allows the generation of two isoforms of endothelial NOS3: NOS3 Glu298 (allele G) and NOS3 Asp298 (allele T) [83]. It is a functional polymorphism, which influences the activity of the enzyme, NO production, blood pressure [17,84], lipid levels [85], and angiogenesis [86] with people with the T allele being particularly homozygous, associated with less enzyme activity [84] and the highest cardiovascular risk [18,19,85], reduced NO bioavailability engaging in the initiation, progression, and complications of atherosclerosis [87] less likely to achieve longevity [16]. These mechanisms can explain what was observed in the present study of the synergistic interaction of NOS3 genotypes with the degree of HT in longevity (Figures 2 and 3) as well as the potentially additive effect of smoking, hypercholesterolemia, obesity, and frequent consumption of red meat (Figure 1).…”

“…Other genes, such as angiotensinogen (AGT), specifically the AGT M235T polymorphism, may be associated with chronic age-associated CVDs [15]. As for NOS3, this is a determinant polymorphism for the production of nitric oxide, with consequent implications for the development of atherosclerosis, hypertension [16,17], and Alzheimer's, with impact on cardiovascular risk and longevity [16,[18][19][20]. Variants of the AT1 receptor of angiotensin II (AGTR1) [21] and other genetic polymorphisms such as the G protein-coupled receptor kinase 4 (GRK4) [22,23] and solute carrier family 12 member 3, SLC12A3 [24], have been related to arterial hypertension and atherosclerosis.…”