Licorice-induced hypertension and common variants of genes regulating renal sodium reabsorption

Ann Med. 2010 Sep;42(6):465-74. doi: 10.3109/07853890.2010.499133.

Abstract

Aim: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics*
  • Adolescent
  • Adult
  • Aldosterone / blood
  • Epithelial Sodium Channels / genetics*
  • Female
  • Genetic Variation
  • Glycyrrhiza / adverse effects*
  • Humans
  • Hypertension / blood
  • Hypertension / chemically induced*
  • Hypertension / genetics
  • Kidney / metabolism
  • Male
  • Middle Aged
  • Mineralocorticoid Excess Syndrome, Apparent / blood
  • Mineralocorticoid Excess Syndrome, Apparent / chemically induced*
  • Mineralocorticoid Excess Syndrome, Apparent / genetics
  • Mutagenesis, Insertional
  • Potassium / blood
  • Renin / blood
  • Sodium / metabolism
  • Young Adult

Substances

  • Epithelial Sodium Channels
  • Aldosterone
  • Sodium
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • HSD11B2 protein, human
  • Renin
  • Potassium