Genetic factors associated with endothelial dysfunction affect the early onset of coronary artery disease in Korean males

Abstract

Abstract:The maintenance of balance between nitric oxide (NO) and the superoxide anion is required for proper functioning of the endothelium. To investigate the relationship between genetic factors associated with endothelial function and the development of coronary artery disease (CAD), endothelial nitric oxide synthase (ecNOS) gene a/b polymorphism and NADH/NADPH oxidase p22 phox gene C242T polymorphism were examined in 305 Korean male CAD patients and 215 healthy male control subjects. The ␤-fibrinogen gene H1/H2 polymorphism was also analyzed. Both ecNOS a/b and p22 phox C242T polymorphisms were found to be associated with the development of CAD in the study population (p = 0.020 and 0.011, respectively). When the association was analyzed by age, statistical significance was retained only in those Ͻ51 years (p = 0.021 and 0.025 for the a/b and the C242T polymorphism, respectively) and not in those Ͼ51 years of age (p =0.155 and 0.278 respectively). However, the distribution of the ␤-fibrinogen H1/H2 genotypes was not found to be associated with the development of CAD in either the Յ50 (p = 0.611) or Ͼ50 groups (p = 0.188). The ecNOS gene a/b polymorphism and the NADH/NADPH oxidase p22 phox gene C242T polymorphism were found to be significantly associated with the development of CAD in Korean male patients less than 51 years old.

Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease

“…Of the 16, 9 showed an increased risk in individuals homozygous for the a allele compared with b allele carriers (b/b plus b/a), 10,11,35,38,39,41,[43][44][45] but only 1 was statistically significant 43 (Figure 3). With a fixed-effect model, the summary OR for IHD among homozygotes for the intron-4a allele was 1.34 (95% CI, 1.03 to 1.75; Pϭ0.03) (Figure 3).…”

The Role of Endothelial Nitric Oxide Synthase Gene Polymorphism in Clinically Classified Patients with Coronary Artery Disease

“…Yoon et al (42) also identified an association of this polymorphism with the risk (20) suggested that enoS polyporphism was significantly associated with the development of CAD in Korea. An interesting aspect of the results from our study is that they conflict with a study of the same gene polymorphism performed in a different part of turkey (23).…”

Detailing Peripheral Arterial Tonometry in Heart Failure. An Endothelial Function Evaluation

“…[45][46][47][48] The ecNOS gene a/b polymorphism and the β-Nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase p22 phox gene C242T polymorphism are found to be significantly associated with the development of CAD. 45,46 Regarding this topic, the following reduce NO bioavailability: polymorphisms in the eNOS gene, 47 upregulation of matrix metalloproteinase-2,49 and elevated levels of dimethylarginine, which is a competitive antagonist of endothelial nitric oxide synthase (eNOS). Some studies also found microRNA 217 upregulation, an NAD-dependent deacetylase, as responsible for endothelial alteration and eNOS activity decrease.…”

“…[30][31][32] Experimental and clinical studies have provided new data about the mechanisms of specific aspects of endothelial function, therefore a potential mechanism of endothelial dysfunction is alteration of the signaling mechanisms involved in eNOS activation. 45 Some novel approaches in patients with polymorphisms or mutations of genes that might play a pathogenic role in endothelial dysfunction investigate the relationship between genetic factors associated with endothelial function and the development of cardiac alterations. [45][46][47][48] The ecNOS gene a/b polymorphism and the β-Nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase p22 phox gene C242T polymorphism are found to be significantly associated with the development of CAD.…”

“…45 Some novel approaches in patients with polymorphisms or mutations of genes that might play a pathogenic role in endothelial dysfunction investigate the relationship between genetic factors associated with endothelial function and the development of cardiac alterations. [45][46][47][48] The ecNOS gene a/b polymorphism and the β-Nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase p22 phox gene C242T polymorphism are found to be significantly associated with the development of CAD. 45,46 Regarding this topic, the following reduce NO bioavailability: polymorphisms in the eNOS gene, 47 upregulation of matrix metalloproteinase-2,49 and elevated levels of dimethylarginine, which is a competitive antagonist of endothelial nitric oxide synthase (eNOS).…”