Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus - PubMed (original) (raw)
Meta-Analysis
doi: 10.1038/ng.79. Epub 2008 Jan 20.
Anna-Karin Abelson, Jerome Wojcik, Ammar Zaghlool, M V Prasad Linga Reddy, Elena Sanchez, Iva Gunnarsson, Elisabet Svenungsson, Gunnar Sturfelt, Andreas Jönsen, Lennart Truedsson, Bernardo A Pons-Estel, Torsten Witte, Sandra D'Alfonso, Nadia Barizzone, Maria Giovanna Danieli, Carmen Gutierrez, Ana Suarez, Peter Junker, Helle Laustrup, Maria Francisca González-Escribano, Javier Martin, Hadi Abderrahim, Marta E Alarcón-Riquelme
Affiliations
- PMID: 18204447
- DOI: 10.1038/ng.79
Meta-Analysis
Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
Sergey V Kozyrev et al. Nat Genet. 2008 Feb.
Erratum in
- Nat Genet. 2008 Apr;40(4):484. Barrizzone, Nadia [corrected to Barizzone, Nadia]
Abstract
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance. 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 x 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 (Delta2), 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.
Comment in
- The developing mosaic of autoimmune disease risk.
Maier LM, Hafler DA. Maier LM, et al. Nat Genet. 2008 Feb;40(2):131-2. doi: 10.1038/ng0208-131. Nat Genet. 2008. PMID: 18227869 No abstract available.
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