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Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations
  1. Ana M Valdes (ana.valdes{at}kcl.ac.uk)
  1. King's College London, United Kingdom
    1. Tim D Spector (tim.spector{at}kcl.ac.uk)
    1. King's College London, United Kingdom
      1. Sally Doherty (sally.doherty{at}nottingham.ac.uk)
      1. Academic Rheumatology, University of Nottingham, City Hospital, United Kingdom
        1. Margaret Wheeler (maggie.wheeler{at}nottingham.ac.uk)
        1. Academic Rheumatology, University of Nottingham, City Hospital, United Kingdom
          1. Deborah J Hart (deborah.hart{at}kcl.ac.uk)
          1. King's College London, United Kingdom
            1. Michael Doherty (michael.doherty{at}nottingham.ac.uk)
            1. Academic Rheumatology, University of Nottingham, City Hospital, United Kingdom

              Abstract

              Objective: Variants in the growth differentiation factor-5 (GDF5) and in the double von Willebrand factor A (DVWA) have been recently reported to be associated with osteoarthritis (OA) in Asian populations. The aim of the current study was to assess the role of such variants in OA susceptibility in two independent UK samples of Caucasian origin.

              Methods: Polymorphisms rs11718863 and rs7639618 (DVWA) and rs143383 (GDF5) were genotyped in 999 knee OA cases, 843 hip OA cases, and 1166 controls from two UK studies from Nottingham and Chingford.

              Results: In agreement with previous reports, the major allele at rs143383 (GDF5) was associated with higher risk of knee OA in our samples (ORMH= 1.29 95% CI 1.14-1.47 p=8 x 10-5). Conversely, the major allele at the DVWA SNP rs7639618, which increased risk in Asians, was not associated with risk of knee OA, (ORMH =0.88 95% CI 0.74-1.03; p=0.12). A meta-analysis of Asian and UK knee OA data indicated highly significant heterogeneity (I2=92% Q=48.5 p=7 x10-10) and no significant association with knee OA using a random effects meta-analysis (ORDL= 1.18 95%CI 0.86-1.63; p=0.309).

              Conclusions: Our data confirm that the GDF5 variant is consistently associated with risk of knee OA. We found considerable ethnic variation in allele frequencies at the DVWA gene and no significant association in UK samples nor combining UK to Asian samples. Our results suggest that the effect that DVWA amino acid changes have on tubulin binding is unlikely to influence risk of OA in Caucasians.

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