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

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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.

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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.

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