HUMAN ALPHA-ADDUCIN GENE, BLOOD-PRESSURE, AND SODIUM-METABOLISM

The adducin genes contribute significantly to population variation in rat blood pressure and cell membrane sodium transport. The 460Trp muta tion of the human alpha-adducin gene has been associated with hyperten sion, in particular hypertension sensitive to sodium restriction. We s tudied the relationship between the 460Trp mutation and population var iation in blood pressure and sodium metabolism. From 603 Scottish fami lies, we selected 151 offspring and 224 parents with blood pressures i n either the upper thigh) or bottom (low) 30% of the population distri bution and measured the 460Trp mutation using allele-specific hybridiz ation. In offspring, we also measured exchangeable sodium, plasma volu me, and total body water. Plasma levels of components of the renin-ang iotensin system, atrial natriuretic peptide, and cellular sodium and t ransmembrane sodium efflux were also estimated, The overall frequency of the 460Trp mutation was 27.1%. In offspring and parent groups, we f ound no difference in the genotype or allele frequencies of the 460Trp mutation between subjects with high or low blood pressure. There was no overall association between the alpha-adducin genotypes and blood p ressure variation, In offspring, the 460Trp mutation was not associate d with any significant differences in body fluid volumes or exchangeab le sodium; levels of plasma renin, angiotensin II, aldosterone, or atr ial natriuretic peptide; intracellular sodium; or ouabain-sensitive tr ansmembrane sodium efflux. These findings suggest that in our Scottish population, the alpha-adducin 460Trp polymorphism is not related to b lood pressure and does not affect whole body or cellular sodium metabo lism.