Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
(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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https://lup.lub.lu.se/record/1198907
- author
- organization
- publishing date
- 2008
- 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}}, }