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ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Authors :
Christos Rossios
Tufail Bashir
Marcus Achison
Simon Adamson
Asangaedem Akpan
Terry Aspray
Alison Avenell
Margaret M Band
Louise A Burton
Vera Cvoro
Peter T Donnan
Gordon W Duncan
Jacob George
Adam L Gordon
Celia L Gregson
Adrian Hapca
Cheryl Hume
Thomas A Jackson
Simon Kerr
Alixe Kilgour
Tahir Masud
Andrew McKenzie
Emma McKenzie
Harnish Patel
Kristina Pilvinyte
Helen C Roberts
Avan A Sayer
Karen T Smith
Roy L Soiza
Claire J Steves
Allan D Struthers
Divya Tiwari
Julie Whitney
Miles D Witham
Paul R Kemp
Source :
PLoS ONE, Vol 18, Iss 10, p e0292402 (2023)
Publication Year :
2023
Publisher :
Public Library of Science (PLoS), 2023.

Abstract

BackgroundAngiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study.MethodsSarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables.ResultsAllele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo.ConclusionOur results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
18
Issue :
10
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.8651c39bcec645eeb9cc2a0bb488cd15
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0292402&type=printable