Letter abstract
Nature Genetics 40, 211 - 216 (2008)
Published online: 20 January 2008 | Corrected online: 27 March 2008 | doi:10.1038/ng.79
There is a Corrigendum (April 2008) associated with this Letter.
Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
Sergey V Kozyrev1,15, Anna-Karin Abelson1,15, Jerome Wojcik2, Ammar Zaghlool1, M V Prasad Linga Reddy1, Elena Sanchez3, Iva Gunnarsson4, Elisabet Svenungsson4, Gunnar Sturfelt5, Andreas Jönsen5, Lennart Truedsson6, Bernardo A Pons-Estel7, Torsten Witte8, Sandra D'Alfonso9, Nadia Barizzone9, Maria Giovanna Danieli10, Carmen Gutierrez11, Ana Suarez11, Peter Junker12, Helle Laustrup12, Maria Francisca González-Escribano13, Javier Martin3,14, Hadi Abderrahim2 & Marta E Alarcón-Riquelme1
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance1, 2, 3. In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 
10-10; OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (
2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point–site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell–receptor signaling and B-cell hyperactivity characteristic of this disease.
- Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden.
- Merck Serono, Chemin des Mines, Geneva 12202, Switzerland.
- Instituto de Biomedicina López-Neyra, Granada 18100, Spain.
- Department of Medicine, Unit of Rheumatology, Karolinska University Hospital, Solna 17176, Sweden.
- Department of Rheumatology, University of Lund, Lund 22200, Sweden.
- Department of Clinical Immunology and Microbiology, University of Lund, Lund 22200, Sweden.
- Sanatorio Parque, Rosario 2000, Argentina.
- Medical School Hannover, Hannover 30625, Germany.
- Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara 13100, Italy.
- Dipartimento di Scienze Mediche e Chirurgiche, Università Politecnica delle Marche, Ancona 60121, Italy.
- Department of Functional Biology, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo 33006, Spain.
- Department of Internal Medicine C, Section of Rheumatology, Odense University Hospital, Odense 5000, Denmark.
- Departamento de Inmunología, Hospital Virgen del Rocío, Sevilla 41013, Spain.
- Consejo Superior de Investigaciones Científicas (CSIC), Grenada 18100, Spain.
- These authors contributed equally to this work.
Correspondence to: Marta E Alarcón-Riquelme1 e-mail: marta.alarcon@genpat.uu.se
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