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

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.

N1 - Funding Information: This work was supported by a Nuffield Foundation Oliver Bird Rheumatism Programme PhD Studentship to R.N.J. Genotyping was funded by Generation Scotland: Genetic Health in the 21st Century (Scottish Funding Council Strategic Research Development Grant HR03006).

PY - 2012/1

Y1 - 2012/1

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 a-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 a-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 - ACTN3

KW - Falls

KW - Genetic association

KW - Skeletal muscle

UR - https://www.scopus.com/pages/publications/79951609727

U2 - 10.1093/gerona/glq189

DO - 10.1093/gerona/glq189

M3 - Article

C2 - 20966103

AN - SCOPUS:79951609727

SN - 1079-5006

VL - 66 A

SP - 130

EP - 135

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

IS - 1

ER -