Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

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; Christos Rossios; 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

doi:10.1371/journal.pone.0294330

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

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 MasudAndrew McKenzie, Emma McKenzie, Harnish Patel, Kristina Pilvinyte, Helen C. Roberts, Christos Rossios, 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^*

^*Corresponding author for this work

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia.

Methods: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial.

Results: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% p_adj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone.

Conclusion: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

Original language	English
Article number	e0294330
Number of pages	18
Journal	PLoS ONE
Volume	18
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0294330
Publication status	Published - 14 Nov 2023

Bibliographical note

Funding:
Funding: The LACE trial (project reference 13/53/03) was funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (https://www.nihr.ac.uk/explore-nihr/funding-programmes/efficacy-and-mechanism-evaluation.htm). The Principal Investigator of the award was MW with PK, AS, AA, PD as co applicants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health and Social Care. AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. The authors acknowledge support from the NIHR Ageing Clinical Research Network and the NHS Scotland Support for Science programme.

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Bashir, T., Achison, M., Adamson, S., Akpan, A., Aspray, T., Avenell, A., Band, M. M., Burton, L. A., Cvoro, V., Donnan, P. T., Duncan, G. W., George, J., Gordon, A. L., Gregson, C. L., Hapca, A., Hume, C., Jackson, T. A., Kerr, S., Kilgour, A., ... Kemp, P. R. (2023). Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial. PLoS ONE, 18(11), Article e0294330. https://doi.org/10.1371/journal.pone.0294330

@article{a8c128fe1a97469b9907a5e5c44bf72d,

title = "Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial",

abstract = "Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. Methods: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. Results: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. Conclusion: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.",

author = "Tufail Bashir and Marcus Achison and Simon Adamson and Asangaedem Akpan and Terry Aspray and Alison Avenell and Band, {Margaret M.} and Burton, {Louise A.} and Vera Cvoro and Donnan, {Peter T.} and Duncan, {Gordon W.} and Jacob George and Gordon, {Adam L.} and Gregson, {Celia L.} and Adrian Hapca and Cheryl Hume and Jackson, {Thomas A.} and Simon Kerr and Alixe Kilgour and Tahir Masud and Andrew McKenzie and Emma McKenzie and Harnish Patel and Kristina Pilvinyte and Roberts, {Helen C.} and Christos Rossios and Sayer, {Avan A.} and Smith, {Karen T} and Soiza, {Roy L.} and Steves, {Claire J.} and Struthers, {Allan D.} and Divya Tiwari and Julie Whitney and Witham, {Miles D} and Kemp, {Paul R.}",

note = "Funding: Funding: The LACE trial (project reference 13/53/03) was funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (https://www.nihr.ac.uk/explore-nihr/funding-programmes/efficacy-and-mechanism-evaluation.htm). The Principal Investigator of the award was MW with PK, AS, AA, PD as co applicants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health and Social Care. AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. The authors acknowledge support from the NIHR Ageing Clinical Research Network and the NHS Scotland Support for Science programme.",

year = "2023",

month = nov,

day = "14",

doi = "10.1371/journal.pone.0294330",

language = "English",

volume = "18",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science (PLOS)",

number = "11",

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Bashir, T, Achison, M, Adamson, S, Akpan, A, Aspray, T, Avenell, A, Band, MM, Burton, LA, Cvoro, V, Donnan, PT, Duncan, GW, George, J, Gordon, AL, Gregson, CL, Hapca, A, Hume, C, Jackson, TA, Kerr, S, Kilgour, A, Masud, T, McKenzie, A, McKenzie, E, Patel, H, Pilvinyte, K, Roberts, HC, Rossios, C, Sayer, AA, Smith, KT, Soiza, RL, Steves, CJ, Struthers, AD, Tiwari, D, Whitney, J, Witham, MD & Kemp, PR 2023, 'Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial', PLoS ONE, vol. 18, no. 11, e0294330. https://doi.org/10.1371/journal.pone.0294330

TY - JOUR

T1 - Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

AU - Bashir, Tufail

AU - Achison, Marcus

AU - Adamson, Simon

AU - Akpan, Asangaedem

AU - Aspray, Terry

AU - Avenell, Alison

AU - Band, Margaret M.

AU - Burton, Louise A.

AU - Cvoro, Vera

AU - Donnan, Peter T.

AU - Duncan, Gordon W.

AU - George, Jacob

AU - Gordon, Adam L.

AU - Gregson, Celia L.

AU - Hapca, Adrian

AU - Hume, Cheryl

AU - Jackson, Thomas A.

AU - Kerr, Simon

AU - Kilgour, Alixe

AU - Masud, Tahir

AU - McKenzie, Andrew

AU - McKenzie, Emma

AU - Patel, Harnish

AU - Pilvinyte, Kristina

AU - Roberts, Helen C.

AU - Rossios, Christos

AU - Sayer, Avan A.

AU - Smith, Karen T

AU - Soiza, Roy L.

AU - Steves, Claire J.

AU - Struthers, Allan D.

AU - Tiwari, Divya

AU - Whitney, Julie

AU - Witham, Miles D

AU - Kemp, Paul R.

N1 - Funding: Funding: The LACE trial (project reference 13/53/03) was funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (https://www.nihr.ac.uk/explore-nihr/funding-programmes/efficacy-and-mechanism-evaluation.htm). The Principal Investigator of the award was MW with PK, AS, AA, PD as co applicants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health and Social Care. AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. The authors acknowledge support from the NIHR Ageing Clinical Research Network and the NHS Scotland Support for Science programme.

PY - 2023/11/14

Y1 - 2023/11/14

N2 - Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. Methods: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. Results: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. Conclusion: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

AB - Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. Methods: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. Results: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. Conclusion: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

U2 - 10.1371/journal.pone.0294330

DO - 10.1371/journal.pone.0294330

M3 - Article

SN - 1932-6203

VL - 18

JO - PLoS ONE

JF - PLoS ONE

IS - 11

M1 - e0294330

ER -

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

Abstract

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