Methylene tetrahydrofolate reductase (MTHFR) and nitric oxide synthase (ecNOS) genes and risks of peripheral arterial disease and coronary heart disease: Edinburgh artery study

Hyperhomocysteinaemia and reduced nitric oxide synthesis may each result in endothelial dysfunction predisposing to atherogenesis. Genetic variants of methylene tetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase (ecNOS) influence homocysteine metabolism and nitric oxide synthes is, respectively and might thus be determinants of the risk of atherosclero tic disease. The aim of our study was to identify, in a general population sample, the risks of peripheral arterial disease and of coronary heart dise ase related to MTHFR (175;198) and ecNOS (4;5) polymorphisms. In the Edinbu rgh Artery Study, which is a population based cohort study, 940 men and wom en aged 60-79 years, who had previously been selected at random from the ge neral population, had DNA extracted from a venous blood sample. Based on a clinical examination at baseline and follow up investigations, three groups of subjects were identified: those with peripheral arterial disease (n = 8 0), those with coronary heart disease (n = 137), and healthy controls who h ad no evidence of cardiovascular disease (n = 300). The distributions of th e ecNOS and MTHFR genotypes did not differ significantly between the groups with and without cardiovascular disease. However, the ecNOS-4 allele (freq uency 0.13) was related to the occurrence of coronary heart disease in non smokers, OR = 2.47 (95% CI [1.42, 4.34], P = 0.02). No association was foun d with peripheral arterial disease. The MTHFR-175 allele (frequency 0.31) w as not related to coronary heart disease, but was associated with a reduced risk of peripheral arterial disease, OR = 0.54 (95% CI [0.32, 0.90], P = 0 .02). Neither the ecNOS-4 allele or MTHFR-175 allele was related to the ank le brachial pressure index in the whole study population. In conclusion, th e ecNOS-4 allele was associated with a slightly increased risk of coronary heart disease in non-smokers, but otherwise the MTHFR and ecNOS genotypes a ppeared to have little influence on the risks of peripheral arterial diseas e and coronary heart disease in this older population. (C) 2000 Elsevier Sc ience Ireland Ltd. All rights reserved.