Plasma Nitric Oxide Concentrations and Nitric Oxide Synthase Gene Polymorphisms in Coronary Artery Disease

Abstract

Background: Plasma NOx (nitrate and nitrite) is a stable end product of the vasodilator NO. Several polymorphisms in the endothelial constitutive NO synthase (ecNOS) gene have been reported, including the 4a/4b VNTR polymorphism in intron 4, the E298D mutation in exon 7, and the G10-T polymorphism in intron 23. The aims of this study were to examine plasma NOx in patients with coronary artery disease (CAD) and to assess the association between plasma NOx concentrations and the three ecNOS gene polymorphisms. Methods: Plasma NOx was measured in samples from 128 healthy controls and from 110 CAD patients at least 2 months after myocardial infarction. Three genetic polymorphisms that are known or have been suggested to be associated with plasma NOx concentration were also analyzed by PCR-restriction fragment length polymorphism. Results: Median plasma NOx was significantly higher (P <0.001) in CAD patients (95.9 μmol/L) than in controls (73.8 μmol/L). Furthermore, the median plasma NOx was significantly higher (P <0.001) in hypertensive CAD patients (116.0 μmol/L) than in controls and normotensive CAD patients (86.0 μmol/L). The G-allele frequency of the G10-T polymorphism in intron 23 was significantly higher in CAD patients than in controls. Other polymorphisms showed no differences in allelic frequencies among the control and CAD groups. In controls, individuals with the E298D mutation in exon 7 (136.1 μmol/L) showed significantly higher (P = 0.001) median plasma NOx than those without this mutation (64.5 μmol/L). Conclusions: Plasma NOx was higher in hypertensive CAD patients than in normotensive CAD patients and controls. The E298D polymorphism of the ecNOS gene was associated with increased plasma NOx. Further study is needed to understand the gene expression and enzyme activity of ecNOS and their association with genotypes.

Plasma Nitrate and Incidence of Cardiovascular Disease and All‐Cause Mortality in the Community: The Framingham Offspring Study

“…Plasma nitrate is frequently considered a measure of the individual overall exposure to nitrate derived from various individual (patho-) physiological pathways and exogenous (ie, dietary) sources, as well as the individual capacity to eliminate nitrate. 2,22,23 Dietary intake of nitrate in the United States is commonly estimated to range between 40 and 100 mg/d, but may exceed 1200 mg with specific diets or dietary supplements. 24,25 High doses of nitrate may be required to significantly increase the plasma nitrate concentration.…”

“…8,17 Therefore, plasma nitrate and/or nitrite are frequently used as surrogates for endogenous NO synthesis and metabolism in clinical studies, 18,31 although a significant contribution to circulating levels from dietary sources has been acknowledged. 1,2,8,22,23,27 Nitrate metabolism by the oral and gastrointestinal microbiome also has to be considered. 8,27,33 In clinical studies, the major part of the oral and gastric microbial nitrate metabolism to nitrite, and possibly NO, was observed shortly after ingestion.…”

Lifestyle and Socioeconomic‐Status Modify the Effects of ADRB2 and NOS3 on Adiposity in European‐American and African‐American Adolescents

“…The-922G>A polymorphism is found in the first intron of NOS3 and is in perfect LD with the -786T<C SNP (21), which has been associated with decreased promoter activity, suppressed eNOS transcription and reduced NO production (31). In addition to that, the presence of the Asp298 allele has been previously associated with reduced (32) or increased (33) endothelial NO production. Although these findings indicate the putative functional implications of these SNPs in adiposity, it is also possible that these two SNPs are in strong LD with functional SNPs elsewhere in the gene.…”

The association between eNOS intron 4 VNTR polymorphism and delayed graft function of kidney allografts

“…The results of our study suggest an association between eNOS VNTR polymorphism and DGF. The majority of previous studies indicate that patients with the eNOS VNTR aa and ab genotypes have lower nitric oxide plasma levels and decreased protein expressions (12,16,17); however, this finding is not supported by all studies (34). It is possible that the a allele is in linkage disequilibrium with other functional variants in regulatory regions of the eNOS gene, leading to decreased nitric oxide synthesis.…”