title: A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension.
abstract: OBJECTIVE
  To determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension.
  
  
  METHODS
  Hypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced.
  
  
  RESULTS
  A previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of aMedicine and bLaboratory Medicine, Groote Schuur Hospital and University of Cape Town, South Africa.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Rayner
authors.forename: E Patricia
authors.initials: EP
authors.lastname: Owen
authors.forename: Judy A
authors.initials: JA
authors.lastname: King
authors.forename: Steven G
authors.initials: SG
authors.lastname: Soule
authors.forename: Heleen
authors.initials: H
authors.lastname: Vreede
authors.forename: Lionel H
authors.initials: LH
authors.lastname: Opie
authors.forename: David
authors.initials: D
authors.lastname: Marais
authors.forename: James S
authors.initials: JS
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood* / Q000235:genetics; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood; D044383:Black People / Q000208:ethnology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006333:Heart Failure / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000235:genetics*; D007008:Hypokalemia / Q000097:blood / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012083:Renin / Q000097:blood* / Q000235:genetics; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*; D013019:South Africa / Q000208:ethnology
chemical_list: D015415:Biomarkers; D015222:Sodium Channels; D000450:Aldosterone; D012083:Renin