R563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype.

BackgroundA 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.MethodsForty-five index patients and members of their kindreds were studied. Blood pressure, serum potassium and the presence of the R563Q mutation were determined.ResultsOf 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.ConclusionThe R563Q mutation of β-ENaC is associated with hypertension within affected kindreds, but does not usually cause the full Liddle’s syndrome phenotype.

The R563Q mutation of the b-subunit of the epithelial sodium channel (ENaC) is associated with hypertension in black and mixed ancestry (MA) men and women in South Africa. The frequency of the R563Q mutation in black and MA women with pre-eclampsia (n = 230) and in controls (n = 198) was studied. The R563Q mutation was found in 7.8% of the women with preeclampsia and in 2.6% of controls (P = 0.014). This remained significant if the black women were analysed separately (P = 0.031). We have demonstrated that a genetic variant of the ENaC is associated with pre-eclampsia. This has implications for understanding the pathogenesis and treatment of pre-eclampsia.Keywords Epithelial sodium channel, pre-eclampsia, R563Q mutation.