alexa Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study.
Orthopaedics

Orthopaedics

Orthopedic & Muscular System: Current Research

Author(s): Vaes RB, Rivadeneira F, Kerkhof JM, Hofman A, Pols HA,

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Abstract 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. This article was published in Ann Rheum Dis and referenced in Orthopedic & Muscular System: Current Research

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