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.
Background and ObjectiveThe aging process affects the responsiveness and other functions of endothelium and vascular smooth muscle cells, predisposing the old vessels to the development of atherosclerotic lesions. Endothelial nitric oxide synthase ecNOS gene polymorphism was shown to affect the occurrence of acute myocardial infarction AMI . We hypothesized that aging may affect the association between the ecNOS gene polymorphism and AMI. Methods We investigated the age-related distribution of the ecNOS gene a/b polymorphism in 121 male AMI patients and 206 age-matched healthy male controls. As a control, we also genotyped b-fibrinogen gene H1/H2 polymorphism in the same population. Results The aa, ab, and bb genotypes were found in 1, 49 and 156 cases among the control subjects and 5, 23 and 93 cases among the AMI patients, respectively. There was a significant association between the ecNOS polymorphism and AMI p 0.045 . When the correlation was analyzed by age, the significance remained only in the group below the age of 51 p 0.009 . The distribution of the b-fibrinogen gene H1/H2 alleles, however, was not found to be associated with development of AMI in both young p 0.7400 and old p 0.2160 population. Conclusion Our results provide the first evidence that links ecNOS polymorphism to the risk of AMI in relation to age. Young persons who smoke or have ecNOS aa genotype may have an increased risk of developing AMI. The functional as well as structural changes associated with aging in the vascular endothelium may mask the effect of the ecNOS polymorphism in the development of AMI in old people.
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