The T allele of the missense Glu298Asp endothelial nitric oxide synthase gene polymorphism is associated with coronary heart disease in younger individuals with high atherosclerotic risk profile

Aims: Nitric oxide (NO) plays a protective role during atherogenesis, In the endothelium, NO is synthesised by the constitutive NO synthase (ecNOS). We analysed the relation of the ecNOS Glu(298)Asp and 4a/b gene polymorphisms to coronary artery disease (CAD) and myocardial infarction (MI) in a population of 3250 German subjects (533 healthy controls and 2717 individuals who underwent coronary angiography). Results: Although in the total sample, the ecNOS T allele was not associated with the risk of CAD (P = 0.054) and the extent of this disease (P = 0.078), a restriction to younger individuals (age less than or equal to 61, mean age) revealed an association of the ecNOS T allele with an increased risk of CAD (1.43, 1.05-1.96; P = 0.025) and with the severity of this disease (P = 0.037). Similar observations were made in various high-risk populations. These associations were even more pronounced when the high-risk subgroups were restricted to younger individuals. For example, an odds ratio of 7.66 for CAD (95% CI, 2.0-29; P = 0.003) was detected in diabetic individuals who were younger than 61 years. Also with respect to MI, the most pronounced associations of the ecNOS T allele with the risk of this disease were detected in younger individuals with at least one other cardiovascular risk factor. For example, in diabetics younger than 61 years, the relative risk for ecNOS T allele carriers was 9.73 (95% CI, 1.8-53; P = 0.008). In contrast, the allele frequencies of the ecNOS 4a/b gene variation were essentially the same in controls and in CAD and MI patients. Conclusion: The present data extends earlier observations by the findings that predominantly younger T allele carriers of the ecNOS Glu(298)Asp gene polymorphism with various coronary high-risk profiles had an increased risk to suffer CAD and/or MI. In contrast, no evidence was found for an association of the ecNOS 4a/b gene polymorphism with coronary heart disease. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.