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

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia - analyses from the LACE randomised controlled trial
Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia - analyses from the LACE randomised controlled trial
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.
1932-6203
Bashir, Tufail
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Achison, Marcus
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Adamson, Simon
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Akpan, Asangaedem
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Aspray, Terry
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Avenell, Alison
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Band, Margaret M.
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Burton, Louise A.
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Cvoro, Vera
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Donnan, Peter T.
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Duncan, Gordon W.
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George, Jacob
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Gordon, Adam L.
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Gregson, Celia L.
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Hapca, Adrian
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Hume, Cheryl
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Jackson, Thomas A.
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Kerr, Simon
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Kilgour, Alixe
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Masud, Tahir
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McKenzie, Andrew
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McKenzie, Emma
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Patel, Harnish
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Pilvinyte, Kristina
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Roberts, Helen C.
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Rossios, Christos
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Sayer, Avan A.
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Smith, Karen T.
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Steves, Claire J.
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Struthers, Allan D.
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Tiwari, Divya
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Whitney, Julie
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Witham, Miles D.
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Kemp, Paul R.
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Bashir, Tufail
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Achison, Marcus
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Adamson, Simon
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Akpan, Asangaedem
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Aspray, Terry
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Avenell, Alison
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Band, Margaret M.
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Burton, Louise A.
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Cvoro, Vera
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Duncan, Gordon W.
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George, Jacob
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Gordon, Adam L.
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Gregson, Celia L.
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Hapca, Adrian
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Jackson, Thomas A.
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Kerr, Simon
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Kilgour, Alixe
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Masud, Tahir
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McKenzie, Andrew
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McKenzie, Emma
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Patel, Harnish
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Pilvinyte, Kristina
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Roberts, Helen C.
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Sayer, Avan A.
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Smith, Karen T.
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Soiza, Roy L.
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Steves, Claire J.
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Struthers, Allan D.
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Tiwari, Divya
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Whitney, Julie
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Witham, Miles D.
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Kemp, Paul R.
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Bashir, Tufail, Achison, Marcus, Adamson, Simon, Akpan, Asangaedem, Aspray, Terry, Avenell, Alison, Band, Margaret M., Burton, Louise A., Cvoro, Vera, Donnan, Peter T., Duncan, Gordon W., George, Jacob, Gordon, Adam L., Gregson, Celia L., Hapca, Adrian, Hume, Cheryl, Jackson, Thomas A., Kerr, Simon, Kilgour, Alixe, Masud, Tahir, McKenzie, Andrew, McKenzie, Emma, Patel, Harnish, Pilvinyte, Kristina, Roberts, Helen C., Rossios, Christos, Sayer, Avan A., Smith, Karen T., Soiza, Roy L., Steves, Claire J., Struthers, Allan D., Tiwari, Divya, Whitney, Julie, Witham, Miles D. and Kemp, Paul 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), [e0294330]. (doi:10.1371/journal.pone.0294330).

Record type: Article

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.

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Accepted/In Press date: 26 October 2023
e-pub ahead of print date: 14 November 2023
Additional Information: Funding Information: 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-mechanismevaluation.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.

Identifiers

Local EPrints ID: 484787
URI: http://eprints.soton.ac.uk/id/eprint/484787
ISSN: 1932-6203
PURE UUID: 803c2870-5abf-4acd-bb97-b14ce0a73b3e
ORCID for Harnish Patel: ORCID iD orcid.org/0000-0002-0081-1802
ORCID for Helen C. Roberts: ORCID iD orcid.org/0000-0002-5291-1880

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Date deposited: 21 Nov 2023 17:53
Last modified: 11 May 2024 01:41

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Contributors

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

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