RT Journal Article
SR Electronic
T1 Genetic variation in the <em>GDF5</em> region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1754
OP 1760
DO 10.1136/ard.2008.099655
VO 68
IS 11
A1 R B A Vaes
A1 F Rivadeneira
A1 J M Kerkhof
A1 A Hofman
A1 H A P Pols
A1 A G Uitterlinden
A1 J B J van Meurs
YR 2009
UL http://ard.bmj.com/content/68/11/1754.abstract
AB Background: A polymorphism (rs143383; T to C) near the GDF5 gene has been associated with height and osteoarthritis (OA), but debate exists about whether its primary biological action is directed to cartilage or bone.Objective: To study the association between genetic variation in the GDF5 region and radiographic osteoarthritis (ROA) susceptibility, height, bone size parameters and fracture risk in a large population-based cohort of Caucasian elderly subjects.Methods: 6365 men and women had genotype data available. ROA was defined as a Kellgren/Lawrence (K/L) score ⩾2 for hand, knee and hip joints. CTX-II levels, height, bone mineral density (BMD), bone size and fracture risk were also assessed.Results: rs143383 and three highly correlated single nucleotide polymorphisms (SNPs) in the GDF5 region were found to be independently associated with OA, height, bone size and fracture risk in women. Women with homozygotes for the rs143383 C allele had a 37% lower risk for hand OA (p = 8×10−6) and a 28% lower risk for knee OA (p = 0.003). In addition, they were 1.1 cm taller (p = 0.001), had a larger hip axis length (HAL) (p = 4×10−4) and had a 29% increased risk of incident non-vertebral fractures (p = 0.02). No associations with hip OA or BMD were detected. No associations were found in men.Conclusion: This population-based study shows that GDF5 gene variants are associated with hand OA, knee OA and fracture risk in elderly women. It also replicates previous association between GDF5 variation and height. Furthermore, our findings for HAL suggest that GDF5 action is primarily directed to the long bones, rather than the axial skeleton.