Meta-analyses of genes modulating intracellular T3 bio-availability reveal a possible role for the DIO3 gene in osteoarthritis susceptibility
- 19 August 2010
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 70 (1), 164-167
- https://doi.org/10.1136/ard.2010.133660
Abstract
Objective To study whether common genetic variants of the genes involved in the complex regulatory mechanism determining the intracellular bio-availability of T3 influence osteoarthritis onset. Methods In total 17 genetic variants within the genes encoding WD40-repeat/SOCS-box protein 1, ubiquitin specific protease 33, thyroid hormone receptor α, deiodinase, iodothyronine, type III (DIO3) and Indian hedgehog were measured and associated with osteoarthritis in a meta-analyses in European populations from the UK, The Netherlands, Greece and Spain containing a total of 3252 osteoarthritis cases and 2132 controls. Results The minor allele of the DIO3 variant rs945006 showed suggestive evidence for protective association in the overall meta-analyses, which was supported by individual osteoarthritis studies and osteoarthritis subtypes. The association appeared most significant in cases with knee and/or hip with an allelic OR of 0.81 (95% CI 0.70 to 0.930) with a nominal p value of 0.004 and a permutation-based corrected p value for multiple testing of 0.039. Conclusion The findings suggest that the DIO3 gene modulates osteoarthritis disease risk; however, additional studies are necessary to replicate our findings. To elucidate the molecular mechanisms focus should be on the local adaptation to T3 availability either during the endochondral ossification process or during ageing of the articular cartilage.Keywords
This publication has 12 references indexed in Scilit:
- The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetesNature Genetics, 2009
- Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling1Endocrine Reviews, 2008
- A Common Variation in Deiodinase 1 Gene DIO1 Is Associated with the Relative Levels of Free Thyroxine and TriiodothyronineJournal of Clinical Endocrinology & Metabolism, 2008
- Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritisHuman Molecular Genetics, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- Further evidence of the role of frizzled-related protein gene polymorphisms in osteoarthritisAnnals Of The Rheumatic Diseases, 2007
- Asporin and knee osteoarthritis in patients of Greek originOsteoarthritis and Cartilage, 2006
- Efficiency and power in genetic association studiesNature Genetics, 2005
- Evidence for familial aggregation of hand, hip, and spine but not knee osteoarthritis in siblings with multiple joint involvement: the GARP studyAnnals Of The Rheumatic Diseases, 2004
- Quantifying heterogeneity in a meta-analysisStatistics in Medicine, 2002