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 (Lead / Corresponding author)

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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% 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.
Original languageEnglish
Article numbere0294330
Number of pages18
JournalPLoS ONE
Volume18
Issue number11
DOIs
Publication statusPublished - 14 Nov 2023

Keywords

  • Sarcopenia
  • Activin receptor
  • polymorphism
  • body composition
  • fat mass
  • height

ASJC Scopus subject areas

  • General

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