The functional HERG variant 897T is associated with Conn's adenoma.
OBJECTIVE
Aldosterone secreting adenomas (aldosteronomas) have an unknown molecular origin. Ion channel currents are involved in signal transduction leading to aldosterone synthesis and secretion. HERG (human-ether-a-go-go-related gene) encodes for a potassium channel responsible for the outward rectifying delayed current and it is mutation prone. When mutated it causes most of the familial forms of both long QT and short QT syndromes. Abnormal repolarization in glomerulosa cells might increase aldosterone secretion or induce a proliferative advantage. The aims of this study were to: (1) evaluate HERG expression in aldosteronomas; (2) search for HERG somatic mutations; and (3) determine whether there is any relationship between the common HERG functional variant (A2690C, leading from lysine 897 to threonine, K897T) and aldosteronoma.


METHODS
Aldosteronoma and blood samples from 17 patients were studied to evaluate HERG expression, full-length HERG complementary DNA sequencing, and genotyping for K897T alleles. The prevalence of HERG 897 alleles was also tested in a control population and a population consisting entirely of hypertensive individuals.


RESULTS
HERG was expressed in all aldosteronomas analysed. HERG somatic mutations were not detected. The 897T variant of HERG was significantly more common among patients with aldosteronoma (897T allele 41%) than in patients with moderate-severe essential hypertension (897T allele 20%, P = 0.007) or in the control population (897T allele 12%, P < 0.0001). The 897T/T genotype was present in 24% of the aldosteronoma patients versus 7% (P = 0.040) and 3% (P = 0.001) in essential hypertension and in the control population, respectively. When the chi test was performed considering the three groups together, the significance was similar (for alleles P < 0.0001 and for genotypes P = 0.004).


CONCLUSIONS
The common functional HERG variant 897T may predispose to the development of aldosteronoma.
Department of Internal Medicine, Università Politecnica delle Marche, Ancona, Italy. r.sarzani@univpm.it
Riccardo
R
Sarzani
Francesca
F
Pietrucci
Christian
C
Corinaldesi
Matteo
M
Francioni
Claudio
C
Letizia
Emilio
E
D'Erasmo
Paolo
P
Dessì-Fulgheri
Alessandro
A
Rappelli
D018246:Adrenocortical Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology* / Q000235:genetics; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA
D051638:Ether-A-Go-Go Potassium Channels