Genetic variability of the ET-1 and the ETA receptor genes in essential hypertension.

Because evidence suggests that endothelin-1 (ET-1) plays a role in the pathogenesis of hypertension, we examined the variability within the ET-1 and the ET(A) receptor genes in patients with essential hypertension (EH). Genomic DNA was used for amplification of both genes by PCR. Polymorphisms within these genes were identified by single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing. Single-base insertions (C at position 121; A at position 138) were identified in the untranslated region of exon 1 of the ET-1 gene. The C insertion was invariant, whereas the A insertion, which abolished a BsiY1 restriction site, occurred only in samples that showed altered mobility profiles on SSCP analysis. This strategy also identified a silent polymorphism in codon 323 (CAC-->CAT) of the ET(A) receptor gene, which created an AflII restriction site. The frequency distribution of these polymorphisms was compared in an EH population [diastolic blood pressure (DBP) > or = 95 mm Hg; n = 100] and a matched normotensive (NT) group (BP < or = 140/85 mm Hg). No significant differences in AflII genotype distribution were found between the EH and NT groups. However, chi 2 analysis suggested a significant difference between the BsiY1+/+, BsiY1-/+, and BsiY1-/- genotype frequencies in the two groups (EH 58:38:4%; NT 47:44:9% (p = 0.045)). In addition, two-way analysis showed a strong correlation between DBP and the BsiY1-/- polymorphism. These results suggest that these polymorphisms act as markers for the level of DBP.