GENETIC-VARIABILITY OF THE ET-1 AND THE ET(A) 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 hypertens ion (EH). Genomic DNA was used for amplification of both genes by PCR. Polymorphisms within these genes were identified by single-strand con formation polymorphism (SSCP) analysis and subsequent DNA sequencing. Single-base insertions (C at position 121; A at position 138) were ide ntified in the untranslated region of exon 1 of the ET-1 gene. The C i nsertion was invariant, whereas the A insertion, which abolished a Bsi Y1 restriction site, occurred only in samples that showed altered mobi lity profiles on SSCP analysis. This strategy also identified a silent polymorphism in codon 323 (CAC --> CAT) of the ET(A) receptor gene, w hich created an AflII restriction site. The frequency distribution of these polymorphisms was compared in an EH population [diastolic blood pressure (DBP) greater than or equal to 95 mm Hg; n = 100] and a match ed normotensive (NT) group (BP less than or equal to 140/85 mm Hg). No significant differences in AflII genotype distribution were found bet ween the EH and NT groups. However, chi(2) analysis suggested a signif icant difference between the BsiY1+/ +, BsiY1-/+, and BsiY1-/- genotyp e 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 DB P and the BsiY1-/- polymorphism. These results suggest that these poly morphisms act as markers for the level of DBP.