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

Figures & data

Table I. Characteristics of the study group at the time of the initial episode of licorice-induced hypertension and during the present study. All laboratory values at the time of licorice-induced hypertension are based on the availability of previous medical records. Values are mean ± SEM.

Variable	Initial episode of hypertension	Present study
Females/males (n)	23/7	23/7
Age (range) years	37.8 ± 2.8 (13–64)	43.8 ± 2.7 (14–66)
BMI, kg/m^2	ND	25.3 ± 0.8 (n = 30)
Antihypertensive medication	5	13
Blood pressure	n = 30	n = 30
Systolic, mmHg	201 ± 4	134 ± 4
Diastolic, mmHg	118 ± 2	82 ± 2
Serum sodium, mmol/L (reference values 137–149)	142.6 ± 0.7 (n = 14)	140.8 ± 0.6 (n = 17)
Serum potassium, mmol/L (reference values 3.7–5.3)	3.2 ± 0.1 (n = 16)	4.2 ± 0.1 (n = 17)
Plasma renin activity, μg/L/h (reference values 2–5)^a	0.1 ± 0.03 (n = 4)	1.2 ± 0.4 (n = 14)
Serum aldosterone, pmol/L (reference values 183–940)	213.7 ± 0.1 (n = 4)	392.3 ± 80.5 (n = 15)

^aTwo subjects with high plasma renin activity, i.e. 40 and 34 μg/L/h, were excluded from the analysis due to possible effect of currently used angiotensin converting enzyme inhibitors.

ND = not determined.

Table II. Characteristics of the subjects with α-, β-, or γENaC gene variants during the present study. Current licorice consumption could not be excluded for subjects 1 and 6.

Subject	1	2	3	4	5	6
Gender/Age	F/20	F/57	F/56	F/65	F/52	F/35
ENaC variation	αInsG	αInsG	βG589S	β- i12 C/T	β- i12 C/T	γV546I
Antihypertensive medication	Yes	No	Yes	Yes	Yes	Yes
Family history of hypertension	Yes	Yes	Yes	Yes	Yes	Yes
Body mass index (kg/m^2)	20.4	24.9	37.3	31.2	26.5	32.8
Blood pressure (mmHg)
Licorice-induced	200/130	180/108	207/140	210/140	180/115	230/136
During the present study	155/90	125/71	140/90	170/90	120/75	120/85
Sodium, mmol/L (reference values 137–149)	141	138	136	142	144	138
Potassium, mmol/L (reference values 3.7–5.3)	3.7	3.4	3.7	4.1	4.3	4.8
Plasma renin, μg/L/h (reference values 2–5)	0.3	2.8	0.3	1.3	ND	0.2
Serum aldosterone, pmol/L (reference values 183–940	<68	910	307	1000	371	<68

ND = not determined.

Figure 1. Partial amino acid sequence of the wild-type αENaC (αENaC wt) and predicted amino acid sequence corresponding to the αENaC G insertion mutation. The mutation affects the carboxy-terminal codon (corresponding to proline residue 669) predicted to result in insertion of 61 amino acids (underlined). Only sequences corresponding to the carboxy-terminal parts (starting from the PPPXY motif, indicated by a box) are shown. In silico prediction revealed a putative protein kinase C phosphorylation site (asterisk), a putative casein kinase II phosphorylation site (square), and a cysteine predicted to form a disulfide bond (triangle).

Figure 2. The pedigrees of the two families with the αENaC G insertion mutation. The probands are shown by arrow (the probands of Families I and II are the Subjects 1 and 2 of Table II, respectively). The ages are given as recorded at the time of the present study (ht+ = treatment-requiring hypertension; ht− = no hypertension; ht(+) = elevated blood pressure without antihypertensive treatment; ? = blood pressure status unknown; ND = not determined; Ren = plasma renin, μg/L/h; Aldo = serum aldosterone, pmol/L; K = potassium, mmol/L).