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 journalArticlepeer-review


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)130-5
Number of pages6
JournalJournals of Gerontology Series A - Biological Sciences and Medical Sciences
Issue number1
Publication statusPublished - Jan 2011


  • Accidental Falls
  • Actinin/genetics
  • Aged
  • Cohort Studies
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Muscle, Skeletal/physiology
  • Polymorphism, Genetic
  • Risk


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