Published Online
on September 25, 2006

A more recent version of this article appeared on November 1, 2006

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Submitted on April 26, 2006
Revised on May 16, 2006

Circulating Activities of Angiotensin-Converting Enzyme, Its Homolog, Angiotensin-Converting Enzyme 2, and Neprilysin in a Family Study

Gillian I. Rice^*; Amy L. Jones; Peter J. Grant; Angela M. Carter; Anthony J. Turner; and Nigel M. Hooper

From the Proteolysis Research Group (G.I.R., A.L.J., A.J.T., N.M.H.), Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics Health and Therapeutics, (G.I.R., A.L.J., P.J.G., A.M.C.), University of Leeds, Leeds, United Kingdom.

^* To whom correspondence should be addressed. E-mail: bmbgir{at}bmb.leeds.ac.uk.

Abstract--The renin-angiotensin system is a key regulator of blood pressure (BP), with inhibitors of angiotensin-converting enzyme (ACE) used clinically to treat hypertension and other cardiovascular conditions. ACE2 is a newly identified member of this system, which converts angiotensin II to angiotensin (1-7), and of which the occurrence in plasma has not been investigated. The aim of this study was to determine the heritability of circulating ACE, ACE2, and neprilysin (NEP), which may also be a regulator of BP, in a family study, and to determine covariates that contribute to the variation in plasma activity. ACE, ACE2, and NEP activities were measured in plasma from 534 subjects in the Leeds Family Study using selective fluorogenic substrates. Genetic factors accounted for 24.5%, 67%, and 22.7% of the phenotypic variation in circulating ACE, ACE2, and NEP, respectively. ACE insertion/deletion polymorphism and other measured covariates accounted for 23.8% of variance in circulating ACE. High-density lipoprotein cholesterol was a significant determinant of circulating ACE2. Measured covariates accounted for 17.3% of variation in circulating NEP. ACE and NEP were associated with systolic and diastolic BP in univariate analyses; however, only ACE was independently associated with systolic and diastolic BP after accounting for covariates and shared childhood household.

Key words: angiotensin • blood pressure • genetics • metalloproteinases • population

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