Polymorphic differences from normal in the aldosterone synthase gene (CYP11B2) in patients with primary hyperaldosteronism and adrenal tumour (Conn'ssyndrome)

OBJECTIVE The hypertension of Conn's syndrome is due to autonomous aldoster one 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 altere d rate of aldosterone secretion. DESIGN In a series (n = 27) of well-characterized Conn's syndrome cases, th e aldosterone synthase gene (CYP11B2) was screened by single-strand conform ational polymorphism (SSCP) for differences from the consensus sequence. RESULTS No new mutations were found. The frequencies of two previously desc ribed linked polymorphisms, one a change of -344C to T in a putative steroi dogenic 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. T he 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. CONCLUSION While it is unlikely that this difference from normal is related to tumour growth, these genotypes may predispose the tumour to aldosterone production.