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


CONCLUSIONS
This study reports for the first time that the functional ACTN3 R577X genotype represents a genetic risk factor for falling in older females.
Judson
Robert N
RN
Musculoskeletal Research Programme, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Wackerhage
Henning
H
Hughes
Alun
A
Mavroeidi
Alexandra
A
Barr
Rebecca J
RJ
Macdonald
Helen M
HM
Ratkevicius
Aivaras
A
Reid
David M
DM
Hocking
Lynne J
LJ
D000058:Accidental Falls; D000185:Actinin / Q000235:genetics* / Q000502:physiology; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D011110:Polymorphism, Genetic; D012306:Risk
C118456:ACTN3 protein, human; D000185:Actinin