title: Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and loss of the insertion allele in aldosterone-producing adenoma.
abstract: 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 pathophysiology of these tumours. Angiotensin-converting enzyme (ACE) catalyses the generation of angiotensin II, and the insertion/deletion (I/D) polymorphism of the ACE gene regulates up to 50% of plasma and cellular 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-unresponsive 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 peripheral blood DNA in the 55 patients with APA. The frequency of the D allele was 0.518 and 0.512 and the I allele was 0.482 and 0.488 in the APA and control subjects respectively. Genotypic and allelic frequency analysis found no significant differences between the groups. Examination of the matched tumour and peripheral blood DNA samples revealed the loss of the insertion allele in four of the 25 patients who were heterozygous for the ACE I/D genotype. The I/D polymorphism of the ACE gene does not appear to contribute to the biochemical and phenotypic characteristic of APA, however, the deletion of the insertion allele of the 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.
authors.affiliation: University of Queensland, Department of Medicine, Greenslopes Hospital, Brisbane, Australia.
authors.forename: T J
authors.initials: TJ
authors.lastname: Tunny
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: K A
authors.initials: KA
authors.lastname: Richardson
authors.forename: M
authors.initials: M
authors.lastname: Stowasser
authors.forename: M
authors.initials: M
authors.lastname: Gartside
authors.forename: R D
authors.initials: RD
authors.lastname: Gordon
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000483:Alleles; D017353:Gene Deletion; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D007703:Peptidyl-Dipeptidase A