MULTILOCUS LINKAGE OF FAMILIAL HYPERKALEMIA AND HYPERTENSION, PSEUDOHYPOALDOSTERONISM TYPE-II, TO CHROMOSOMES 1Q31-42 AND 17P11-Q21

Essential hypertension is a common multifactorial trait. The molecular basis of a number of rare diseases that alter blood pressure in human s has been established, identifying pathways that may be involved in m ore common forms of hypertension(1). Pseudohypoaldosteronism type II ( PHAII, also known as familial hyperkalaemia and hypertension or Gordon 's syndrome; OMIM #145260), is characterized by hyperkalaemia despite normal renal glomerular filtration, hypertension and correction of phy siologic abnormalities by thiazide diuretics(2,3). Mild hyperchloremia , metabolic acidosis and suppressed plasma renin activity are variable associated findings. The pathogenesis of PHAII is unknown, although c linical studies indicate an abnormality in renal ion transport(4). As thiazide diuretics are among the most efficacious agents in the treatm ent of essential hypertension, understanding the pathogenesis of PHAII may be of relevance to more common forms of hypertension. Analysis of linkage in eight PHAII families showing autosomal dominant transmissi on demonstrates locus heterogeneity of this trait, with a multilocus l od score of 8.1 for linkage of PHAII to chromosomes 1q31-q42 and 17p11 -q21. Interestingly, the chromosome-17 locus overlaps a syntenic inter val in rat that contains a blood pressure quantitative trait locus (QT L). Our findings provide a first step toward identification of the mol ecular basis of PHAII.