PRELIMINARY EVIDENCE OF LINKAGE OF SALT SENSITIVITY IN BLACK-AMERICANS AT THE BETA(2)-ADRENERGIC RECEPTOR LOCUS

Salt sensitivity is a heritable trait that is a hallmark of hypertensi on in black Americans. Genes encoding adrenergic receptors are candida te loci for the inheritance of this hypertension-related trait because of the role of these receptors in the regulation of renal sodium excr etion and vascular tone. We performed this study to determine whether these loci are responsible for some of the phenotypic variation in sal t sensitivity. Hypertensive black American probands were ascertained, followed by sequential ascertainment of adult sib pairs among the firs t-, second- and third-degree relatives of the proband. Both hypertensi ve and normotensive siblings were tested for salt sensitivity by an in travenous sodium-loading, lasix volume-depletion protocol. Genotyping was performed with restriction fragment length polymorphisms in genomi c DNA probed with clones containing the beta(2)- and alpha(2c10)-adren ergic receptor genes. A total of 109 sib pairs was evaluated. Salt sen sitivity was defined as the change in blood pressure in each individua l, comparing the sodium-loaded with the volume-depleted state. Systoli c pressure decreased by an average of 9.0 +/- 9%, diastolic pressure b y 1.5 +/- 11%, and mean arterial pressure by 5.0 +/- 9%. Neither blood pressure nor salt sensitivity was linked at the alpha(2c10)-adrenergi c receptor locus. No evidence suggested that systolic salt sensitivity and baseline blood pressure were linked at the beta(2)-adrenergic rec eptor locus. Model-independent sib pair linkage analysis suggested tha t diastolic blood pressure response to sodium loading/volume depletion is linked at the beta(2)-adrenergic receptor locus (P<.006). Evidence for linkage was significant at the .05 level after adjustment for the number of phenotypic traits examined.