Herbal Medicine Containing Licorice May Be Contraindicated for a Patient with an HSD11B2 Mutation

Abstract

Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). However, the combined effect of licorice ingestion and an HSD11B2 mutation has never been reported, until now. In this study, we demonstrated that licorice ingestion can produce overt hypertension in an individual without medical history of hypertension who is heterozygous for wild-type and mutant HSD11B2 genes. Our patient was a 51-year-old female with serious hypertension who had been taking herbal medicine containing licorice for more than one year. She was clinically diagnosed as having licorice intoxication, because she did not present with hypertension after ceasing the herbal medicine. Molecular analysis showed that she carried a missense mutation, c.40C>T, in HSD11B2. In conclusion, licorice ingestion is an environmental risk factor for hypertension or AME state in patients with a mutation in HSD11B2. Carrying a mutation in HSD11B2 is, conversely, a genetic risk factor for licorice-induced hypertension or AME state. Herbal medicine containing licorice may, therefore, be contraindicated in patients with an HSD11B2 mutation.

Figure 1

DHPLC screening for a mutation in the HSD11B2 gene. Screening showed a small and large peak on the chromatogram of HSD11B2 exon 1, while controls showed a single peak. The small peak indicated heteroduplex DNA formation, suggesting the presence of a mutation in the patient's HSD11B2 exon 1.

Figure 2

Direct DNA sequencing of HSD11B2 exon 1 (a) and amino acid sequence surrounding the mutation (b). DNA sequencing showed heterozygous status for the wild-type (C at nucleotide position 40) and mutant (T at nucleotide position 40) sequences.

Figure 3

Schematic drawing of the pathogenesis of the patient. The patient was heterozygous for a mutation in HSD11B2 (“normal/mutant" alleles in the figure), suggesting that her 11βHSD2 enzyme activity in the kidney was reduced. Without licorice loading, she was able to keep her healthy condition. However, with licorice loading, she showed serious hypertension.