Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
- Title
- Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
- Author
- 배상철
- Keywords
- Medical and Health Sciences; Medicin och halsovetenskap; MEDICINE; MEDICIN
- Issue Date
- 2011-05
- Publisher
- NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
- Citation
- NATURE GENETICS,43(3),253-U102
- Abstract
- Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
- URI
- http://eds.b.ebscohost.com/eds/detail/detail?vid=0&sid=c755726c-46d7-4f92-87bf-feb4456f1b8c%40sessionmgr103&bdata=Jmxhbmc9a28mc2l0ZT1lZHMtbGl2ZQ%3d%3d#AN=edsswe.oai.DiVA.org.uu.148999&db=edsswehttp://search.proquest.com/docview/856043083?accountid=11283http://hdl.handle.net/20.500.11754/41041
- ISSN
- 1061-4036
- DOI
- 10.1038/ng.766
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML