Abstract
We reported earlier that two mitochondrial gene polymorphisms, UCP2 –866 G/A (rs659366) and mtDNA nt13708 G/A (rs28359178), are associated with multiple sclerosis (MS). Here we aim to investigate whether these functional polymorphisms contribute to other eight chronic inflammatory diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener' granulomatosis (WG), Churg–Strauss syndrome (CSS), Crohn's disease (CD), ulcerative colitis (UC), primary sclerosing cholangitis (PSC) and psoriasis. Compared with individual control panels, the UCP2 –866 G/A polymorphism was associated with RA and SLE, and the mtDNA nt13708 G/A polymorphism with RA. Compared with combined controls, the UCP2 –866 G/A polymorphism was associated with SLE, WG, CD and UC. When all eight disease panels and the original MS panel were combined in a meta-analysis, the UCP2 was associated with chronic inflammatory diseases in terms of either alleles (odds ratio (OR)=0.91, 95% confidence interval (95% CI): 0.86–0.96), P=0.0003) or genotypes (OR=0.88, (95% CI: 0.82–0.95), P=0.0008), with the –866A allele associated with a decreased risk to diseases. As the −866A allele increases gene expression, our findings suggest a protective role of the UCP2 protein in chronic inflammatory diseases.
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Acknowledgements
The authors thank all patients, physicians and volunteer healthy controls for the cooperation. The cooperation of the Deutsche Morbus Crohn und Colitis Vereinigung e.V. and of the contributing gastroenterologists is gratefully acknowledged. The authors thank Rica Waterstadt for assistance in genotyping. This work was supported by grants from EU FP6 (EURO-RA), Hertie Stiftung, German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN), Deutsche Forschungsgemeinschaft (KFO170) and the PopGen Biobank. The project received infrastructure support through the DFG excellence cluster ‘Inflammation at Interfaces’. Benedicte A Lie and the Norwegian Bone Marrow Donor Registry at Rikshospitalet University Hospital, Oslo, are acknowledged for contributing the healthy Norwegian control population.
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Yu, X., Wieczorek, S., Franke, A. et al. Association of UCP2 −866 G/A polymorphism with chronic inflammatory diseases. Genes Immun 10, 601–605 (2009). https://doi.org/10.1038/gene.2009.29
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DOI: https://doi.org/10.1038/gene.2009.29
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