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.

dx.doi.org/10.1136/ard.2008.099655, hdl.handle.net/1765/24882
Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases
This work was funded by the European Commission 7th Framework Programme; grant id fp7/200800 - Translational Research in Europe – Applied Technologies for Osteoarthritis (TREAT OA), This work was funded by the European Commission 7th Framework Programme; grant id fp7/201865 - GENETIC FACTORS FOR OSTEOPOROSIS (GEFOS)
Erasmus MC: University Medical Center Rotterdam

Vaes, R.B.A, Rivadeneira Ramirez, F, Kerkhof, J.M, Hofman, B, Pols, H.A.P, Uitterlinden, A.G, & van Meurs, J.B.J. (2009). Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: The Rotterdam study. Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases, 68(11), 1754–1760. doi:10.1136/ard.2008.099655