Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2024
Historique:
received: 14 05 2024
accepted: 26 06 2024
medline: 2 8 2024
pubmed: 2 8 2024
entrez: 2 8 2024
Statut: epublish

Résumé

Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Identifiants

pubmed: 39093910
doi: 10.1371/journal.pone.0307268
pii: PONE-D-24-19033
doi:

Substances chimiques

Receptor, Bradykinin B2 0
Leucine GMW67QNF9C

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0307268

Informations de copyright

Copyright: © 2024 Shrestha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Auteurs

Alvin Shrestha (A)

Cardiovascular and Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom.
Cutrale Perioperative and Ageing Group, Department of Bioengineering, Imperial College London, London, United Kingdom.

Tufail Bashir (T)

Cardiovascular and Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom.

Marcus Achison (M)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Simon Adamson (S)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Asangaedem Akpan (A)

Liverpool University Hospitals NHS FT Trust, Clinical Research Network Northwest Coast, University of Liverpool, Liverpool, United Kingdom.

Terry Aspray (T)

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Cumbria Northumberland Tyne and Wear NHS Foundation Trust and Newcastle upon Tyne Hospitals NHS Trust, Translational Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Alison Avenell (A)

Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom.

Margaret M Band (MM)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Louise A Burton (LA)

Medicine for the Elderly, NHS Tayside, Dundee, United Kingdom.
Ageing and Health, University of Dundee, Dundee, United Kingdom.

Vera Cvoro (V)

Victoria Hospital, Kirkcaldy, United Kingdom.
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Peter T Donnan (PT)

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, United Kingdom.

Gordon W Duncan (GW)

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Medicine for the Elderly, NHS Lothian, Edinburgh, United Kingdom.

Jacob George (J)

Division of Molecular & Clinical Medicine, University of Dundee Medical School, Ninewells Hospital, Dundee, United Kingdom.

Adam L Gordon (AL)

Unit of Injury, Inflammation and Recovery, School of Medicine, University of Nottingham, Nottingham United Kingdom.
NIHR Nottingham Biomedical Research Centre, Department of Medicine for the Elderly, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, United Kingdom.

Celia L Gregson (CL)

Musculoskeletal Research Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Older Person's Unit, Royal United Hospital NHS Foundation Trust Bath, Bath, United Kingdom.

Adrian Hapca (A)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Cheryl Hume (C)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Thomas A Jackson (TA)

Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.

Simon Kerr (S)

Department of Older People's Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

Alixe Kilgour (A)

Medicine for the Elderly, NHS Lothian, Edinburgh, United Kingdom.
Ageing and Health Research Group, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.

Tahir Masud (T)

Clinical Gerontology Research Unit, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, United Kingdom.

Andrew McKenzie (A)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Emma McKenzie (E)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Harnish Patel (H)

NIHR Biomedical Research Centre, University of Southampton and University Hospital Southampton NHSFT, Southampton, Hampshire, United Kingdom.

Kristina Pilvinyte (K)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Helen C Roberts (HC)

Academic Geriatric Medicine, Mailpoint 807 Southampton General Hospital, University of Southampton, Southampton, United Kingdom.

Avan A Sayer (AA)

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Cumbria Northumberland Tyne and Wear NHS Foundation Trust and Newcastle upon Tyne Hospitals NHS Trust, Translational Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Christos Rossios (C)

Cardiovascular and Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom.

Karen T Smith (KT)

Tayside Clinical Trials Unit (TCTU), Tayside Medical Science Centre (TASC), Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.

Roy L Soiza (RL)

Ageing & Clinical Experimental Research (ACER) Group, University of Aberdeen, Aberdeen, United Kingdom.

Claire J Steves (CJ)

Department of Twin Research and Genetic Epidemiology, King's College London & Department of Clinical Gerontology, King's College Hospital, London, United Kingdom.

Allan D Struthers (AD)

Division of Molecular & Clinical Medicine, University of Dundee Medical School, Ninewells Hospital, Dundee, United Kingdom.

Divya Tiwari (D)

Bournemouth University and Royal Bournemouth Hospital, Bournemouth, United Kingdom.

Julie Whitney (J)

School of Population Health & Environmental Sciences, King's College London and King's College Hospital, London, United Kingdom.

Miles D Witham (MD)

AGE Research Group, NIHR Newcastle Biomedical Research Centre, Cumbria Northumberland Tyne and Wear NHS Foundation Trust and Newcastle upon Tyne Hospitals NHS Trust, Translational Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Paul R Kemp (PR)

Cardiovascular and Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom.

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Classifications MeSH