Licorice-induced hypertension and common variants of genes regulating renal sodium reabsorption.
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.
Miettinen
Helena E
HE
Department of Medicine, University of Helsinki, Helsinki, Finland. Helena.Miettinen@hus.fi
Piippo
Kirsi
K
Hannila-Handelberg
Tuula
T
Paukku
Kirsi
K
Hiltunen
Timo P
TP
Gautschi
Ivan
I
Schild
Laurent
L
Kontula
Kimmo
K
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
D053503:Epithelial Sodium Channels; D000450:Aldosterone; D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D012083:Renin; D011188:Potassium