Objective: A polymorphism (rs143383; T to C) near the GDF5 gene has been associated with height and osteoarthritis (OA), but debate exists whether its primary biological action is directed to cartilage or bone. We studied 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.
Methods: In total, 6,365 men and women had genotype data available. ROA was defined as a Kellgren/Lawrence (K/L) score ≥2 for hand, knee and hip joints. We also assessed CTX-II levels, height, bone mineral density (BMD), bone size and fracture risk.
Results: We observed the rs143383 and three highly correlated SNPs in the GDF5 region to be independently associated with OA, height, bone size and fracture risk in women. Female homozygotes for the rs143383 C-allele had a 37% lower risk for hand OA (p=8x10-6) and a 28% lower risk for knee OA (p=0.003). In addition, they were 1.1cm taller (p=0.001), had a larger hip axis length (HAL) (p=4x10-4), and had a 29% increased risk of incident nonvertebral fractures (p=0.02). No associations with hip OA or BMD were detected. No associations were observed 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 on HAL suggest that GDF5 action is primarily directed to the long bones, rather than the axial skeleton.