| Literature DB >> 23473037 |
Anna Biason-Lauber1, Marianne Böni-Schnetzler2, Basil P Hubbard3, Karim Bouzakri4, Andrea Brunner2, Claudia Cavelti-Weder2, Cornelia Keller2, Monika Meyer-Böni1, Daniel T Meier2, Caroline Brorsson5, Katharina Timper2, Gil Leibowitz6, Andrea Patrignani7, Remy Bruggmann7, Gino Boily8, Henryk Zulewski2, Andreas Geier9, Jennifer M Cermak10, Peter Elliott10, James L Ellis10, Christoph Westphal10, Urs Knobel2, Jyrki J Eloranta11, Julie Kerr-Conte12, François Pattou12, Daniel Konrad13, Christian M Matter14, Adriano Fontana15, Gerhard Rogler9, Ralph Schlapbach7, Camille Regairaz16, José M Carballido16, Benjamin Glaser6, Michael W McBurney8, Flemming Pociot5, David A Sinclair3, Marc Y Donath2.
Abstract
Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to β cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.Entities:
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Year: 2013 PMID： 23473037 PMCID： PMC3746172 DOI： 10.1016/j.cmet.2013.02.001
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287