Journal Article

Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues

Bovée, Judith V M G, van Dalen, Wouter J, Meulenbelt, Ingrid, Raine, Emma V A, Bos, Steffan D, Nelissen, Rob G H H, Slagboom, P Eline, Duijnisveld, Bouke J, Loughlin, John, van der Breggen, Ruud, Ramos, Yolande F M

2012

Overview

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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group,Elsevier Limited
• Subject: Adult / Aged / Aged, 80 and over / Arthritis / Biological and medical sciences / Biomedical research / Cartilage, Articular - enzymology / Consortia / Deoxyribonucleic acid / Diseases of the osteoarticular system / DNA / Female / Gene expression / Genetic Predisposition to Disease / Genetic testing / Humans / Immunohistochemistry / Iodide Peroxidase - genetics / Iodide Peroxidase - metabolism / Iodothyronine Deiodinase Type II / Loss of Heterozygosity / Male / Medical sciences / Middle Aged / Osteoarthritis, Hip - enzymology / Osteoarthritis, Hip - genetics / Osteoarthritis, Hip - pathology / Osteoarthritis, Knee - enzymology / Osteoarthritis, Knee - genetics / Osteoarthritis, Knee - pathology / Polymorphism, Single Nucleotide / Proteins / Ratios / Risk Factors / Severity of Illness Index / Thyroid gland