title: Licorice-induced hypertension and common variants of genes regulating renal sodium reabsorption.
abstract: OBJECTIVE
  To study if gene alterations affecting renal sodium reabsorption associate with susceptibility to licorice-induced hypertension.
  
  
  METHODS
  Finnish subjects (n = 30) with a previously documented incident of licorice-induced hypertension were recruited for the study using a newspaper announcement. Their previous clinical and family histories as well as serum electrolyte levels were examined. DNA samples from all individuals were screened for variants of the genes encoding 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) and alpha-, beta-, and gamma-subunits of the epithelial sodium channel (ENaC).
  
  
  RESULTS
  Upon licorice predisposition, the patients had a mean blood pressure of 201/118 mmHg. Circulating potassium, renin, and aldosterone levels were low. No significant DNA variations were identified in the 11betaHSD2 gene. Four subjects were heterozygous for beta- and gammaENaC variants previously shown to be associated with hypertension. Furthermore, a novel G insertion (2004-2005insG) in the SCNN1A gene encoding the alphaENaC was identified in two subjects. The frequency of these ENaC variants was significantly higher in subjects with licorice-induced hypertension (6/30 i.e. 20%) than in blood donors (11/301 i.e. 3.7%, P = 0.002).
  
  
  CONCLUSIONS
  Defects of the 11betaHSD2 gene do not constitute a likely cause for licorice-induced hypertension. Variants of the ENaC subunits may render some individuals sensitive to licorice-induced metabolic alterations and hypertension.
authors.affiliation: Department of Medicine, University of Helsinki, Helsinki, Finland. Helena.Miettinen@hus.fi
authors.forename: Helena E
authors.initials: HE
authors.lastname: Miettinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Piippo
authors.forename: Tuula
authors.initials: T
authors.lastname: Hannila-Handelberg
authors.forename: Kirsi
authors.initials: K
authors.lastname: Paukku
authors.forename: Timo P
authors.initials: TP
authors.lastname: Hiltunen
authors.forename: Ivan
authors.initials: I
authors.lastname: Gautschi
authors.forename: Laurent
authors.initials: L
authors.lastname: Schild
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006035:Glycyrrhiza / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D043204:Mineralocorticoid Excess Syndrome, Apparent / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D016254:Mutagenesis, Insertional; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D055815:Young Adult
chemical_list: D053503:Epithelial Sodium Channels; D000450:Aldosterone; D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D012083:Renin; D011188:Potassium