Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: findings from the LACE sarcopenia trial
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Introduction
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.
Methods
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. Partici pants’ blood samples were genotyped for rs179972 using TaqMan and rs5810761 by ampli fication through Hotstar Taq. Genotypes were compared with outcomes of physical
performance and body composition measures.
Results
Data from 136 individuals were included in the analysis. For rs1799722 the genotype fre quency (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).
Conclusion
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.
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.
Methods
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. Partici pants’ blood samples were genotyped for rs179972 using TaqMan and rs5810761 by ampli fication through Hotstar Taq. Genotypes were compared with outcomes of physical
performance and body composition measures.
Results
Data from 136 individuals were included in the analysis. For rs1799722 the genotype fre quency (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).
Conclusion
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.
Editor(s)
De Rui, Marina
Date Issued
2024-08-02
Date Acceptance
2024-06-26
Citation
PLoS One, 2024, 19 (8)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS One
Volume
19
Issue
8
Copyright Statement
© 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.
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.
License URL
Identifier
http://dx.doi.org/10.1371/journal.pone.0307268
Publication Status
Published
Article Number
e0307268
Date Publish Online
2024-08-02