ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study.

Luiz Cavalcante,Lannie O’Keefe,Jia Li,Shanie Landen,David J. Bishop,Jujiao Kuang,Sarah Voisin,Oren Tirosh,Nir Eynon,Macsue Jacques,Noam Dvir,Ioannis D. Papadimitriou,Xu Yan,Fiona Munson,Andrew Garnham

doi:10.1152/japplphysiol.00344.2018

Abstract

Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort ( n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood ( P < 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 < P < 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE ( P < 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE ( P < 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle. NEW & NOTEWORTHY This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content.

Highlights

Angiotensin-converting enzyme (ACE) is a key enzyme of the renin-angiotensin system (RAS)
The aims of this study were to investigate whether 1) the ACE I/D gene variant is associated with physiological characteristics [such as peak oxygen uptake (V O2peak), lactate threshold (LT), power peak (Wpeak)] at baseline (i.e.; preexercise); 2) the ACE I/D gene variant is associated with ACE content in blood, and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline; and 3) the ACE I/D gene variant is associated with ACE enzyme content changes in blood and ACE, UCP2, and UCP3 protein content changes in muscle following a single session of high-intensity interval exercise (HIIE)
ACE I/D Gene Variant Is Not Associated with Baseline Fitness Levels

Summary

Introduction

Angiotensin-converting enzyme (ACE) is a key enzyme of the renin-angiotensin system (RAS). ACE is expressed in skeletal muscle [18] and is associated with increased blood pressure and glucose homeostasis [11]. The I allele was reported to be associated with endurance performance in highaltitude mountaineers [24]. This association between I allele and endurance capacity was subsequently replicated in elite athletes [25, 27]. Danser et al [8] showed that carriers of the D allele have higher ACE enzyme activity in the heart. It is, unclear whether the ACE I/D gene polymorphism influences the ACE protein content in human skeletal muscle

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