INSERTION DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING ENZYME GENE AND LOSS OF THE INSERTION ALLELE IN ALDOSTERONE-PRODUCING ADENOMA/

The genetic mechanisms responsible for the formation of adrenocortical adenomas which autonomously produce aldosterone are largely unknown, The adrenal renin-angiotensin system has been implicated in the pathop hysiology of these tumours, Angiotensin-converting enzyme (ACE) cataly ses the generation of angiotensin II, and the insertion/deletion (I/D) polymorphism of the ACE gene regulates up to 50% of plasma and cellul ar ACE variability in humans. We therefore examined the genotypic and allelic frequency distributions of the ACE gene I/D polymorphism in 55 patients with aldosterone-producing adenoma, APA, (angiotensin-unresp onsive APA n = 28, angiotensin-responsive APA n = 27), and 80 control subjects with no family history of hypertension, We also compared the ACE gene I/D polymorphism allelic pattern in matched tumour and periph eral blood DNA in the 55 patients with APA, The frequency of the D all ele was 0.518 and 0.512 and the I allele was 0.482 and 0.488 in the AP A and control subjects respectively, Genotypic and allelic frequency a nalysis found no significant differences between the groups, Examinati on of the matched tumour and peripheral blood DNA samples revealed the loss of the insertion allele in four of the 25 patients who were hete rozygous for the ACE I/D genotype. The I/D polymorphism of the ACE gen e does not appear to contribute to the biochemical and phenotypic char acteristics of APA, however, the deletion of the insertion allele of t he ACE gene I/D polymorphism in 16% of aldosterone-producing adenomas may represent the loss of a tumour suppressor gene/s or other genes on chromosome 17q which may contribute to tumorigenesis in APA.