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

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24 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.

Original languageEnglish
Pages (from-to)130-135
Number of pages6
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume66A
Issue number1
DOIs
Publication statusPublished - Jan 2011

Keywords

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

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