Evaluation of heterodimeric guanylyl cyclase genes as candidates for human hypertension

Abstract

Both physiologic and pharmacological data have implicated the nitric oxide (NO) signaling cascade in the regulation of blood pressure in humans and its impairment in the pathogenesis of hypertension. In biological systems, the principal receptor for NO is NO-stimulated guanylyl cyclase. NO-stimulated guanylyl cyclases are obligate heterodimers (alpha/beta). The genes for guanylyl cyclase subunits alpha1, beta, and beta2 are likely candidates for causing hypertension in the Dahl rat as their expression is altered and their gene loci are closely linked to known quantitative trait loci for blood pressure in Dahl rat crosses. The objective of the current study was to test whether markers near guanylyl cyclase subunit genes were linked to hypertension in Caucasians. To test for linkage of genetic markers in or near the guanylyl cyclase genes to hypertension in Caucasians, a sample of 124 Utah hypertensive sib pairs was genotyped. Four highly polymorphic markers in or near the human guanylyl cyclase subunits homologous to the rat alpha1 (human chromosome 8), rat beta1 (human chromosome 4), and rat beta2 (human chromosome 13) genes showed no evidence of excess allele sharing in the set of hypertensive sibships. We conclude that the heterodimeric guanylyl cyclase subunit loci do not appear to be linked to hypertension in Caucasians.