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 are 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 susceptibility loci in both a rat model and human hypertensives, we investigated whether the thiazide-sensitive Na,Cl-cotransporter (TSC) gene contributes to hypertension susceptibility in a rat F2 intercross and in a northern Sardinian human cohort for polygenic hypertension.


METHODS
The rat TSC (rTSC) gene was analyzed directly for cosegregation with salt-sensitive hypertension in an F2 (Dahl S x Dahl R) rat population (n = 102) characterized for blood pressure by radiotelemetry. The human TSC (hTSC) gene was analyzed for association with hypertension in a human hypertensive cohort from northern Sardinia that consisted of 220 unrelated normotensives and 254 unrelated hypertensives. The TSC gene was subjected to single locus and digenic (in combination with ATP1A1 and NKCC2 genes) analyses in both rat and human cohorts.


RESULTS
In both rat model and human cohorts, the rTSC and hTSC genes did not show linkage or association with high blood pressure, respectively. Furthermore, interaction with either ATP1A1 or NKCC2 was not detected in both the rat F2 intercross and human hypertension cohorts.


CONCLUSIONS
These data exclude a primary role of the TSC gene in hypertension pathogenesis in the hypertension cohorts studied.
Song
Y
Y
Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Herrera
V L
VL
Filigheddu
F
F
Troffa
C
C
Lopez
L V
LV
Glorioso
N
N
Ruiz-Opazo
N
N
D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D020412:Multifactorial Inheritance; D051381:Rats; D020303:Rats, Inbred Dahl; D011955:Receptors, Drug / Q000235:genetics*; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
D002352:Carrier Proteins; D011955:Receptors, Drug; C578714:SLC12A1 protein, human; C578874:SLC12A3 protein, human; C578716:Slc12a1 protein, rat; C578876:Slc12a3 protein, rat; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D000254:Sodium-Potassium-Exchanging ATPase