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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
  • View Item
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A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5 ' UTR of GDF5 with osteoarthritis susceptibility

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Author
Chapman, K.; Takahashi, A.; Meulenbelt, I.; Watson, C.; Rodriguez-Lopez, J.; Egli, R.; Tsezou, A.; Malizos, K. N.; Kloppenburg, M.; Shi, D. Q.; Southam, L.; van der Breggen, R.; Donn, R.; Qin, J. H.; Doherty, M.; Slagboom, P. E.; Wallis, G.; Kamatani, N.; Jiang, Q.; Gonzalez, A.; Loughlin, J.; Ikegawa, S.
Date
2008
DOI
10.1093/hmg/ddn038
Keyword
OF-RHEUMATOLOGY CRITERIA
ACID-REPEAT POLYMORPHISM
KNEE OSTEOARTHRITIS
HIP OSTEOARTHRITIS
CLINICAL-TRIALS
ASPORIN GENE
RISK-FACTORS
ASSOCIATION
CLASSIFICATION
POPULATION
Biochemistry & Molecular Biology
Genetics & Heredity
Metadata display
Abstract
We have performed a meta-analysis combining data for more than 11 000 individuals. It provides compelling evidence for a positive association between a functional single-nucleotide polymorphism (SNP) in the 5'-UTR of GDF5 (+104T/C; rs143383) and osteoarthritis (OA) in European and Asian populations. This SNP has recently been reported to be associated with OA in Japanese and Han Chinese populations. Attempts to replicate this association in European samples have been inconclusive, as no association was found in the case-control cohorts from the UK, Spain and Greece when studied individually. However, the pooled data of UK and Spain found an association of the T-allele with an odds ratio (OR) of 1.10. Although the European studies had adequate power to replicate the original findings from the Japanese cohort (OR = 1.79), these results suggest that the role of the GDF5 polymorphism may not be as strong in Europeans. To clarify whether the European studies were hampered by insufficient power, we combined new data from the UK and the Netherlands with the three published studies of Europe and Asia. The results provide strong evidence of a positive association of the GDF5 SNP with knee OA for Europeans as well as for Asians. The combined association for both ethnic groups is highly significant for the allele frequency model (P = 0.0004, OR = 1.21) and the dominant model (P < 0.0001, OR = 1.48). These findings represent the first highly significant evidence for a risk factor for the development of OA which affects two highly diverse ethnic groups.
URI
http://hdl.handle.net/11615/26566
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  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ. [19705]
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