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Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues
  1. Steffan D Bos1,2,
  2. Judith V M G Bovée3,
  3. Bouke J Duijnisveld4,
  4. Emma V A Raine5,
  5. Wouter J van Dalen1,
  6. Yolande F M Ramos1,
  7. Ruud van der Breggen1,
  8. Rob G H H Nelissen4,
  9. P Eline Slagboom2,6,
  10. John Loughlin5,
  11. Ingrid Meulenbelt1,2
  1. 1Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands
  3. 3Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
  4. 4Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Newcastle University, Institute of Cellular Medicine, 4th Floor Catherine Cookson Building, The Medical School, Framlington Place, Newcastle upon Tyne, UK
  6. 6Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Steffan Daniël Bos, LUMC, Molecular Epidemiology, Einthovenweg 20, Leiden 2333 ZC, The Netherlands; s.bos{at}lumc.nl

Abstract

Objective Genetic variation at the type II deiodinase (D2) gene (DIO2) was previously identified as osteoarthritis (OA) risk factor. To investigate mechanisms possibly underlying this association, we assessed D2 protein in healthy and OA-affected cartilage and investigated allelic balance of the OA risk polymorphism rs225014 at DIO2 in human OA joints.

Methods Immunohistochemical staining of healthy and OA-affected cartilage was performed for D2. We then assessed allelic balance of DIO2 mRNA within OA-affected cartilage both at and away from the lesion, ligaments and subchondral bone. Allelic balance was measured by the amount of alleles ‘C’ and ‘T’ of the intragenic OA risk polymorphism rs225014 in heterozygous carriers.

Results A markedly higher amount of D2 positive cells and staining intensity was observed in OA cartilage. A significant, 1.3-fold higher presence was observed for the OA-associated rs225014 ‘C’ allele relative to the ‘T’ allele of DIO2, which was significant in 28 of 31 donors.

Conclusion In OA cartilage, D2 protein presence is increased. The allelic imbalance of the DIO2 mRNA transcript, with the OA risk allele ‘C’ of rs225014 more abundant than the wild-type ‘T’ allele in heterozygote carriers provides a possible mechanism by which genetic variation at DIO2 confers OA risk.

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Footnotes

  • Competing interests None.

  • Ethics approval METC Leiden University Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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