Non-association of the thiazide-sensitive Na,Cl-cotransporter gene with polygenic hypertension in both rats and humans

Objective Genes underlying renal regulation of sodium and water balances ar e a priori valid candidates for polygenic hypertension susceptibility genes . Having recently identified the association of alpha1 Na,K-ATPase (ATP1A1) and Na,K,2Cl-cotransporter (NKCC2) as interacting hypertension susceptibil ity loci in both a rat model and human hypertensives, we investigated wheth er the thiazide-sensitive Na,Cl-cotransporter (TSC) gene contributes to hyp ertension susceptibility in a rat F-2 intercross and in a northern Sardinia n human cohort for polygenic hypertension. Subjects and methods The rat TSC (rTSC) gene was analyzed directly for cose gregation with salt-sensitive hypertension in an F-2 (Dahl S x Dahl R) rat population (n = 102) characterized for blood pressure by radiotelemetry. Th e human TSC (hTSC) gene was analyzed for association with hypertension in a human hypertensive cohort from northern Sardinia that consisted of 220 unr elated normotensives and 254 unrelated hypertensives. The TSC gene was subj ected to single locus and digenic (in combination with ATP1A1 and NKCC2 gen es) analyses in both rat and human cohorts. Results In both rat model and human cohorts, the rTSC and hTSC genes did no t show linkage or association with high blood pressure, respectively. Furth ermore, interaction with either ATP1A1 or NKCC2 was not detected in both th e rat F-2 intercross and human hypertension cohorts. Conclusions These data exclude a primary role of the TSC gene in hypertension pathogenesis in the hypertension cohorts studied. (C) 2001 Lippincott Williams & Wilkins.