The R563Q mutation of the epithelial sodium channel beta-subunit is associated with hypertension.
BACKGROUND
A high prevalence of the R563Q mutation of the epithelial sodium channel β-subunit has been reported in South African hypertensives compared with unrelated normotensive controls. To delineate the effects of this mutation against a more uniform genetic background, this study investigated the association of the mutation with hypertension within affected kindreds.


METHODS
Forty-five index patients and members of their kindreds were studied. Blood pressure, serum potassium and the presence of the R563Q mutation were determined.


RESULTS
Of the 136 individuals studied, 89 were heterozygous for the R563Q mutation and 47 homozygous RR. The mean arterial pressure was significantly higher in the R563Q heterozygous group (p = 0.005) after adjusting for gender, race, age and kindred membership. Of the R563Q heterozygous subjects, 71 (80%) had hypertension, while 17 (36%) of the R563Q homozygous RR subjects were hypertensive. Six R563Q heterozygous subjects had hypokalaemia and one R563Q homozygous RR subject had hypokalaemia, but the difference was not statistically significant. Two heterozygous patients had Liddle's syndrome, both occurring during pregnancy.


CONCLUSIONS
The R563Q mutation of β-ENaC is associated with hypertension within affected kindreds, but does not usually cause the full Liddle's syndrome phenotype.
Division of Hypertension, Groote Schuur Hospital and University of Cape Town, South Africa.
E S
ES
Jones
E P
EP
Owen
J S
JS
Davidson
L
L
Van Der Merwe
B L
BL
Rayner
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D004252:DNA Mutational Analysis; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007008:Hypokalemia / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D056929:Liddle Syndrome / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011188:Potassium / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D013019:South Africa; D055815:Young Adult
D053503:Epithelial Sodium Channels; C507048:SCNN1B protein, human; D011188:Potassium