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Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Klinisk farmakogenomik och osteoporos)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Kardiovaskulär epidemiologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2003 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 18, no 3, 11- p.Article 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. 18, no 3, 11- p.
Keyword [en]
Aminopeptidase, irbesartan, hypertension, polymorphism, left ventricular hypertrophy, angiotensin, pharmacogenomics, bradykinin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-65503DOI: 10.1186/1471-2261-3-11PubMedID: 13678427OAI: oai:DiVA.org:uu-65503DiVA: diva2:93414
Available from: 2008-02-22 Created: 2008-02-22 Last updated: 2017-11-30Bibliographically approved

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Hallberg, PärLind, LarsMichaëlsson, KarlLiljedahl, UlrikaSyvänen, Ann-ChristineMelhus, Håkan

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