ACE SPLICE-SITE MUTATION RESULTING IN 5–10-FOLD ELEVATED ACE LEVELS ALTERS NEITHER BASELINE RENIN AND ANGIOTENSIN LEVELS NOR THE RESPONSE TO ACE INHIBITION: PP.24.464:
Journal of Hypertension(2010)
Abstract
Background: Recently, we described a splice site mutation of intron 25 of the ACE gene, associated with a 5–10-fold increase in serum ACE but not resulting in hypertension or overt cardiovascular disease (De Visscher et al., J Hypertens 2008; 26 (S1), p.132). The ACE increase is most likely due to skipping of exon 26, leading to the absence of the transmembrane domain and, thus, increased shedding of ACE into the extracellular fluid. Aim of the Study: To study the effect of this new ACE mutation on components of the renin-angiotensin-aldosterone system (RAAS) in subjects from the initial pedigree with or without the mutation, both under control (baseline) conditions and after ACE inhibition. Methods: Blood was collected at baseline and at 3 and 6 hours post 50 mg captopril per os. Renin and prorenin were measured by immunoradiometric assay, angiotensinogen by enzyme-kinetic assay, and angiotensin (Ang) II and aldosterone by radiomimmunoassay. Results: Baseline renin (7 ± 4 vs. 9 ± 1 ng/L), prorenin (47 ± 16 vs. 46 ± 18 ng/L), angiotensinogen (2232 ± 963 vs. 3575 ± 1812 nmol/L), Ang II (6 ± 2 vs. 8 ± 1 nmol/L), and aldosterone (48 ± 32 vs. 27 ± 1 ng/L) levels were similar in affected and non-affected family members, and the captopril-induced changes in these components (2–3-fold rises in renin, 2–3 fold decreases in Ang II and aldosterone, and no change in prorenin or angiotensinogen) were also identical in both groups. Conclusion: The splice site mutation of the ACE gene described here does not affect circulating RAAS components, nor the response to ACE inhibition. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Ang II generation and its cardiovascular consequences.
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Key words
angiotensin levels,ace inhibition,baseline renin,splice-site
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