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Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus

Abstract

The TNFAIP3 (tumor necrosis factor alpha–induced protein 3) gene encodes a ubiquitin editing enzyme, A20, that restricts NF-κB–dependent signaling and prevents inflammation. We show that three independent SNPs in the TNFAIP3 region (rs13192841, rs2230926 and rs6922466) are associated with systemic lupus erythematosus (SLE) among individuals of European ancestry. These findings provide critical links between A20 and the etiology of SLE.

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Figure 1: TNFAIP3 region showing D′ for genotypes of all study subjects and location of independently associated SNPs.

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Acknowledgements

This work was supported by R01 AR44804 (L.A.C.), K24 AR02175 (L.A.C.), N01 AI95386 (P.K.G.), ABCoN contract NO1-AR-1-2256 (P.K.G.), AR050267 (M.F.S.), the Mary Kirkland Center for Lupus Research (L.A.C.), the Rainin Foundation (A.M.), T32 DK07007 (T.T.L.), U19 AI063603 (P.-Y.K.), 2R01 AR4658805 (S.M.), K24 AR02213 (S.M.), R01 HL 54900 (M.I.K.) and R01 HL 74165 (M.I.K.). These studies were performed in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, US Public Health Service. We also thank the individuals and physicians who contributed DNA samples and clinical data for this study.

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Contributions

S.L.M., K.E.T. and A.M. wrote the manuscript with input from the coauthors. K.E.T., J.N. and M.F.S. performed the analyses. S.L.M., R.C.F. and W.O. performed genotyping of rs2230926. N.S. generated the human cDNA constructs and T.T.L. conducted the functional studies under the supervision of A.M. M.A.P., M.I.K., S.M., P.K.G. and L.A.C. provided samples for this project. T.W.B. and P.K.G. led the project from which the primary SNP data was generated, and A.M., P.-Y.K. and L.A.C. directed the work described in this manuscript.

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Correspondence to Lindsey A Criswell.

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Ricardo C. Ferreira, Ward Ortmann and Timothy W. Behrens are employees of Genentech.

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Supplementary Methods, Supplementary Tables 1–4, Supplementary Figure 1 (PDF 836 kb)

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Musone, S., Taylor, K., Lu, T. et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 40, 1062–1064 (2008). https://doi.org/10.1038/ng.202

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