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 > or =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 x 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 x 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.
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 > or =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 x 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 x 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.
Authors: Thomas H Alexander; August B Sage; Albert C Chen; Barbara L Schumacher; Elliot Shelton; Koichi Masuda; Robert L Sah; Deborah Watson Journal: Tissue Eng Part C Methods Date: 2010-10 Impact factor: 3.056
Authors: Rui Zhang; Jianfeng Yao; Peng Xu; Baohu Ji; James V Luck; Brian Chin; Shemin Lu; John R Kelsoe; Jie Ma Journal: Inflamm Res Date: 2015-04-17 Impact factor: 4.575
Authors: Hanneke J M Kerkhof; Rik J Lories; Ingrid Meulenbelt; Ingileif Jonsdottir; Ana M Valdes; Pascal Arp; Thorvaldur Ingvarsson; Mila Jhamai; Helgi Jonsson; Lisette Stolk; Gudmar Thorleifsson; Guangju Zhai; Feng Zhang; Yanyan Zhu; Ruud van der Breggen; Andrew Carr; Michael Doherty; Sally Doherty; David T Felson; Antonio Gonzalez; Bjarni V Halldorsson; Deborah J Hart; Valdimar B Hauksson; Albert Hofman; John P A Ioannidis; Margreet Kloppenburg; Nancy E Lane; John Loughlin; Frank P Luyten; Michael C Nevitt; Neeta Parimi; Huibert A P Pols; Fernando Rivadeneira; Eline P Slagboom; Unnur Styrkársdóttir; Aspasia Tsezou; Tom van de Putte; Joseph Zmuda; Tim D Spector; Kari Stefansson; André G Uitterlinden; Joyce B J van Meurs Journal: Arthritis Rheum Date: 2010-02