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Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus

Kozyrev, Sergey V ; Abelson, Anna-Karin ; Wojcik, Jerome ; Zaghlool, Ammar ; Reddy, M V Prasad Linga ; Sanchez, Elena ; Gunnarsson, Iva ; Svenungsson, Elisabet ; Sturfelt, Gunnar LU and Jönsen, Andreas LU , et al. (2008) In Nature Genetics 40(2). p.211-216
Abstract
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). 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 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 (Delta 2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594,... (More)
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). 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 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 (Delta 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
40
issue
2
pages
211 - 216
publisher
Nature Publishing Group
external identifiers
  • wos:000252732900020
  • scopus:38649138296
  • pmid:18204447
ISSN
1546-1718
DOI
10.1038/ng.79
language
English
LU publication?
yes
id
c3fc9ef9-bdf9-487b-b35d-f990af451a02 (old id 1198907)
date added to LUP
2016-04-01 14:42:21
date last changed
2022-04-06 20:02:21
@article{c3fc9ef9-bdf9-487b-b35d-f990af451a02,
  abstract     = {{Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). 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 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 (Delta 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.}},
  author       = {{Kozyrev, Sergey V and Abelson, Anna-Karin and Wojcik, Jerome and Zaghlool, Ammar and Reddy, M V Prasad Linga and Sanchez, Elena and Gunnarsson, Iva and Svenungsson, Elisabet and Sturfelt, Gunnar and Jönsen, Andreas and Truedsson, Lennart and Pons-Estel, Bernardo A and Witte, Torsten and D'Alfonso, Sandra and Barrizzone, Nadia and Danieli, Maria Giovanna and Gutierrez, Carmen and Suarez, Ana and Junker, Peter and Laustrup, Helle and Gonzalez-Escribano, Maria Francisca and Martin, Javier and Abderrahim, Hadi and Alarcon-Riquelme, Marta E}},
  issn         = {{1546-1718}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{211--216}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus}},
  url          = {{http://dx.doi.org/10.1038/ng.79}},
  doi          = {{10.1038/ng.79}},
  volume       = {{40}},
  year         = {{2008}},
}