Salt Intake Affects the Relation Between Hypertension and the T-786C Polymorphism in the Endothelial Nitric Oxide Synthase Gene

BACKGROUND: Recent genetic studies have shown an association between the T-786C polymorphism in the endothelial NO synthase gene and coronary artery diseases, but any possible association with hypertension has been controversial. Other studies indicate the effect of restricting salt intake differ depending on individual salt-sensitivity, and the mixture of different sensitivity in study subjects may obscure the results. The objective of this study was to investigate the gene-environment interaction between the salt intake and this polymorphism. METHODS: We genotyped 281 healthy men after excluding 37 men on hypertensive therapy (mean age 44.8 +/- 11.9 years) for the mutation, and evaluated their daily salt intake using a validated food frequency questionnaire. RESULTS: A quartile classification of salt intake revealed that the blood pressure of subjects with the mutation was significantly higher than that of subjects without the mutation, but only in the 4th quartile (the highest intake group). A multiple logistic regression analysis also showed that the presence of this mutation increased the risk of hypertension only in the 4th quartile (adjusted odds ratio = 6.38, P = .025). CONCLUSIONS: The presence of this mutation alone does not significantly increase the risk of hypertension. However, high salt intake interacts with the mutation and leads to a significant increase in the risk of hypertension. The T-786C mutation warrants being considered a candidate for further study with the aim of tailor-made hypertension prevention.