Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study.

Abstract

Endothelin-1 (ET-1) is a potent vasoactive peptide that has been implicated in the regulation of basal vascular tone. Endothelin-converting enzyme-1 (ECE-1), the main enzyme responsible for ET-1 generation, may contribute to blood pressure (BP) control. A possible association between a polymorphism of the gene encoding ECE-1 (ECE1B C-338A) and BP values in untreated hypertensive women was recently reported. We studied the influence of the ECE1B C-338A polymorphism on BP levels in 1189 subjects participating in the Etude du Vieillissement Artériel (EVA study), and looked for an interaction between this variant and a polymorphism of the ET-1 gene (EDN1 K198N). The ECE1B C-338A polymorphism was genotyped in 491 men and 698 women; 477 men and 669 women could also be genotyped for the EDN1 K198N polymorphism. Associations between BP levels and genotypes were assessed by ANOVA; ANCOVA was used to control for covariates. We found an association between the ECE1B C-338A polymorphism and BP levels in women but not in men. Specifically, females homozygous for the A allele had significantly higher systolic, diastolic and mean BP levels (P = 0.01, 0.02, 0.006 respectively, after adjustment for age and body mass index). Genotyping of the EDN1 K198N polymorphism showed that this variant was not associated with BP values in either men or women, but interacted with the ECE1 variant to influence systolic and mean BP levels in women. Results from this large association study suggest that the genes encoding ECE-1 and ET-1 interact to modulate BP levels in women.