Polymorphic differences from normal in the aldosterone synthase gene (CYP11B2) in patients with primary hyperaldosteronism and adrenal tumour (Conn's syndrome).
OBJECTIVE
The hypertension of Conn's syndrome is due to autonomous aldosterone production by a unilateral adrenocortical adenoma. The source of tumour initiation and the reasons for excess aldosterone production as opposed to cortisol are not known, although variations in the promoter region of the gene coding for aldosterone synthase (CYP11B2) might account for the altered rate of aldosterone secretion.


METHODS
In a series (n = 27) of well-characterized Conn's syndrome cases, the aldosterone synthase gene (CYP11B2) was screened by single-strand conformational polymorphism (SSCP) for differences from the consensus sequence.


RESULTS
No new mutations were found. The frequencies of two previously described linked polymorphisms, one a change of -344C to T in a putative steroidogenic factor-1 (SF-1) binding site and the other an exchange of intron 2 for that of CYP11B1 (conversion) were measured in tumour and genomic DNA. The frequency of the SF-1 T allele (P < 0.0001) and the conversion allele (P < 0.001) were markedly different between the Conn's syndrome group and the normal controls. However, the frequency did not differ between tumour and genomic DNA in the patient group.


CONCLUSIONS
While it is unlikely that this difference from normal is related to tumour growth, these genotypes may predispose the tumour to aldosterone production.
Inglis
G C
GC
MRC Blood Pressure Group, Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland and Département d'Hypertension Arterielle, Hôpital Brousais, Paris, France.
Plouin
P F
PF
Friel
E C
EC
Davies
E
E
Fraser
R
R
Connell
J M
JM
D000236:Adenoma / Q000097:blood / Q000235:genetics*; D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2