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Randomized Controlled Trial
. 2024 Aug 2;19(8):e0307268.
doi: 10.1371/journal.pone.0307268. eCollection 2024.

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

Alvin Shrestha  1   2 , Tufail Bashir  1 , Marcus Achison  3 , Simon Adamson  3 , Asangaedem Akpan  4 , Terry Aspray  5 , Alison Avenell  6 , Margaret M Band  3 , Louise A Burton  7   8 , Vera Cvoro  9   10 , Peter T Donnan  11 , Gordon W Duncan  10   12 , Jacob George  13 , Adam L Gordon  14   15 , Celia L Gregson  16   17 , Adrian Hapca  3 , Cheryl Hume  3 , Thomas A Jackson  18 , Simon Kerr  19 , Alixe Kilgour  12   20 , Tahir Masud  21 , Andrew McKenzie  3 , Emma McKenzie  3 , Harnish Patel  22 , Kristina Pilvinyte  3 , Helen C Roberts  23 , Avan A Sayer  5 , Christos Rossios  1 , Karen T Smith  3 , Roy L Soiza  24 , Claire J Steves  25 , Allan D Struthers  13 , Divya Tiwari  26 , Julie Whitney  27 , Miles D Witham  5 , Paul R Kemp  1
Affiliations
Randomized Controlled Trial

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

Alvin Shrestha et al. PLoS One. .

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. 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.

Results: 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).

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
Associations of rs1799722 genotype on (A) six-minute walk distance (6MWD) and (B) leg muscle mass in men and women. Differences across the genotypes were calculated by Kruskall-Walis Test with post hoc analysis of differences between genotypes corrected using Bonferoni adjustment.
Fig 2
Fig 2. Association of rs5810761 genotype on arm fat mass in men and women.
Differences across the genotypes were calculated by Kruskall-Walis Test with post hoc analysis of differences between genotypes corrected using Bonferroni adjustment.
See this image and copyright information in PMC

References

    1. Cruz-Jentoft AJ, Sayer AA. Sarcopenia. The Lancet. 2019. Jun;393(10191):2636–46. - PubMed
    1. Kemp PR, Griffiths M, Polkey MI. Muscle wasting in the presence of disease, why is it so variable? Biol Rev. 2019. Jun;94(3):1038–55. doi: 10.1111/brv.12489 - DOI - PubMed
    1. Powers SK, Morton AB, Hyatt H, Hinkley MJ. The Renin-Angiotensin System and Skeletal Muscle. Exerc Sport Sci Rev. 2018. Oct;46(4):205–14. doi: 10.1249/JES.0000000000000158 - DOI - PMC - PubMed
    1. Brink M, Price SR, Chrast J, Bailey JL, Anwar A, Mitch WE, et al.. Angiotensin II Induces Skeletal Muscle Wasting through Enhanced Protein Degradation and Down-Regulates Autocrine Insulin-Like Growth Factor I. 2001;142(4). doi: 10.1210/endo.142.4.8082 - DOI - PubMed
    1. Du Bois P, Pablo Tortola C, Lodka D, Kny M, Schmidt F, Song K, et al.. Angiotensin II Induces Skeletal Muscle Atrophy by Activating TFEB-Mediated MuRF1 Expression. Circ Res. 2015. Aug 14;117(5):424–36. - PMC - PubMed

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