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Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy
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2003 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, Vol. 3Article in journal (Refereed) Published
Abstract [en]

Background: Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension. Methods: We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing. Results: After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan, those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs - 16.7 [4.5], p = 0.03). Conclusions: The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.

Place, publisher, year, edition, pages
2003. Vol. 3
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-27063DOI: 10.1186/1471-2261-3-11Local ID: 11710OAI: diva2:247614
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-10

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Nyström, Fredrik
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