The functional ACTN3 577X variant increases the risk of falling in older females: results from two large independent cohort studies

Robert N Judson, Henning Wackerhage, Alun Hughes, Alexandra Mavroeidi, Rebecca J Barr, Helen M Macdonald, Aivaras Ratkevicius, David M Reid, Lynne J Hocking

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

BACKGROUND: Falls among elderly people is a major issue in public health, causing debilitating outcomes including fracture. The identification of genetic risk factors for falling may provide a strategy for effectively targeting falls prevention programs. We investigated whether a common functional variant of skeletal muscle α-actinin-3 (ACTN3 p. R577X) previously associated with impairments in muscle strength, power, and physical functioning represents a risk factor for falls.

METHODS: Case-control analysis was conducted using two large cohorts of Caucasian postmenopausal women--the North of Scotland Osteoporosis Study (n = 1,245) and the Aberdeen Prospective Osteoporosis Screening Study (n = 2,918)--for whom self-reported falls status and DNA samples were available. Cross-sectional analysis of fallers versus nonfallers at baseline and follow-up was performed. In addition, individuals who reported having fallen at more than one timepoint (recurrent fallers) were compared with those who reported not falling at any timepoint.

RESULTS: Association between R577X genotype and falls was identified and validated. Carriage of 577X (one or two copies) was significantly associated with a 33% (10%-61%) increased risk of falling, with the effect apparent at both baseline and follow-up assessments (meta-analysis p = .003 and p = .02, respectively). No significant effect on recurrent falls was observed.

CONCLUSION: This study reports for the first time that the functional ACTN3 R577X genotype represents a genetic risk factor for falling in older females.

LanguageEnglish
Pages130-135
Number of pages6
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume66A
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Accidental Falls
Cohort Studies
Osteoporosis
Genotype
Actinin
Muscle Strength
Scotland
Meta-Analysis
Skeletal Muscle
Public Health
Cross-Sectional Studies
DNA

Keywords

  • accidental falls
  • actinin/genetics
  • aged
  • cohort Studies
  • female
  • genotype
  • humans
  • middle aged
  • muscle, skeletal/physiology
  • polymorphism, genetic
  • risk

Cite this

Judson, Robert N ; Wackerhage, Henning ; Hughes, Alun ; Mavroeidi, Alexandra ; Barr, Rebecca J ; Macdonald, Helen M ; Ratkevicius, Aivaras ; Reid, David M ; Hocking, Lynne J. / The functional ACTN3 577X variant increases the risk of falling in older females : results from two large independent cohort studies. 2011 ; Vol. 66A, No. 1. pp. 130-135.
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title = "The functional ACTN3 577X variant increases the risk of falling in older females: results from two large independent cohort studies",
abstract = "BACKGROUND: Falls among elderly people is a major issue in public health, causing debilitating outcomes including fracture. The identification of genetic risk factors for falling may provide a strategy for effectively targeting falls prevention programs. We investigated whether a common functional variant of skeletal muscle α-actinin-3 (ACTN3 p. R577X) previously associated with impairments in muscle strength, power, and physical functioning represents a risk factor for falls.METHODS: Case-control analysis was conducted using two large cohorts of Caucasian postmenopausal women--the North of Scotland Osteoporosis Study (n = 1,245) and the Aberdeen Prospective Osteoporosis Screening Study (n = 2,918)--for whom self-reported falls status and DNA samples were available. Cross-sectional analysis of fallers versus nonfallers at baseline and follow-up was performed. In addition, individuals who reported having fallen at more than one timepoint (recurrent fallers) were compared with those who reported not falling at any timepoint.RESULTS: Association between R577X genotype and falls was identified and validated. Carriage of 577X (one or two copies) was significantly associated with a 33{\%} (10{\%}-61{\%}) increased risk of falling, with the effect apparent at both baseline and follow-up assessments (meta-analysis p = .003 and p = .02, respectively). No significant effect on recurrent falls was observed.CONCLUSION: This study reports for the first time that the functional ACTN3 R577X genotype represents a genetic risk factor for falling in older females.",
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Judson, RN, Wackerhage, H, Hughes, A, Mavroeidi, A, Barr, RJ, Macdonald, HM, Ratkevicius, A, Reid, DM & Hocking, LJ 2011, 'The functional ACTN3 577X variant increases the risk of falling in older females: results from two large independent cohort studies' vol. 66A, no. 1, pp. 130-135. https://doi.org/10.1093/gerona/glq189

The functional ACTN3 577X variant increases the risk of falling in older females : results from two large independent cohort studies. / Judson, Robert N; Wackerhage, Henning; Hughes, Alun; Mavroeidi, Alexandra; Barr, Rebecca J; Macdonald, Helen M; Ratkevicius, Aivaras; Reid, David M; Hocking, Lynne J.

Vol. 66A, No. 1, 01.2011, p. 130-135.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The functional ACTN3 577X variant increases the risk of falling in older females

T2 - results from two large independent cohort studies

AU - Judson, Robert N

AU - Wackerhage, Henning

AU - Hughes, Alun

AU - Mavroeidi, Alexandra

AU - Barr, Rebecca J

AU - Macdonald, Helen M

AU - Ratkevicius, Aivaras

AU - Reid, David M

AU - Hocking, Lynne J

PY - 2011/1

Y1 - 2011/1

N2 - BACKGROUND: Falls among elderly people is a major issue in public health, causing debilitating outcomes including fracture. The identification of genetic risk factors for falling may provide a strategy for effectively targeting falls prevention programs. We investigated whether a common functional variant of skeletal muscle α-actinin-3 (ACTN3 p. R577X) previously associated with impairments in muscle strength, power, and physical functioning represents a risk factor for falls.METHODS: Case-control analysis was conducted using two large cohorts of Caucasian postmenopausal women--the North of Scotland Osteoporosis Study (n = 1,245) and the Aberdeen Prospective Osteoporosis Screening Study (n = 2,918)--for whom self-reported falls status and DNA samples were available. Cross-sectional analysis of fallers versus nonfallers at baseline and follow-up was performed. In addition, individuals who reported having fallen at more than one timepoint (recurrent fallers) were compared with those who reported not falling at any timepoint.RESULTS: Association between R577X genotype and falls was identified and validated. Carriage of 577X (one or two copies) was significantly associated with a 33% (10%-61%) increased risk of falling, with the effect apparent at both baseline and follow-up assessments (meta-analysis p = .003 and p = .02, respectively). No significant effect on recurrent falls was observed.CONCLUSION: This study reports for the first time that the functional ACTN3 R577X genotype represents a genetic risk factor for falling in older females.

AB - BACKGROUND: Falls among elderly people is a major issue in public health, causing debilitating outcomes including fracture. The identification of genetic risk factors for falling may provide a strategy for effectively targeting falls prevention programs. We investigated whether a common functional variant of skeletal muscle α-actinin-3 (ACTN3 p. R577X) previously associated with impairments in muscle strength, power, and physical functioning represents a risk factor for falls.METHODS: Case-control analysis was conducted using two large cohorts of Caucasian postmenopausal women--the North of Scotland Osteoporosis Study (n = 1,245) and the Aberdeen Prospective Osteoporosis Screening Study (n = 2,918)--for whom self-reported falls status and DNA samples were available. Cross-sectional analysis of fallers versus nonfallers at baseline and follow-up was performed. In addition, individuals who reported having fallen at more than one timepoint (recurrent fallers) were compared with those who reported not falling at any timepoint.RESULTS: Association between R577X genotype and falls was identified and validated. Carriage of 577X (one or two copies) was significantly associated with a 33% (10%-61%) increased risk of falling, with the effect apparent at both baseline and follow-up assessments (meta-analysis p = .003 and p = .02, respectively). No significant effect on recurrent falls was observed.CONCLUSION: This study reports for the first time that the functional ACTN3 R577X genotype represents a genetic risk factor for falling in older females.

KW - accidental falls

KW - actinin/genetics

KW - aged

KW - cohort Studies

KW - female

KW - genotype

KW - humans

KW - middle aged

KW - muscle, skeletal/physiology

KW - polymorphism, genetic

KW - risk

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DO - 10.1093/gerona/glq189

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