Title |
Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
|
---|---|
Published in |
Nature Genetics, January 2008
|
DOI | 10.1038/ng.79 |
Pubmed ID | |
Authors |
Sergey V Kozyrev, 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 |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 2% |
United Kingdom | 1 | <1% |
Unknown | 162 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 33 | 20% |
Student > Ph. D. Student | 27 | 16% |
Student > Bachelor | 23 | 14% |
Student > Master | 19 | 11% |
Other | 11 | 7% |
Other | 32 | 19% |
Unknown | 22 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 51 | 31% |
Medicine and Dentistry | 40 | 24% |
Biochemistry, Genetics and Molecular Biology | 25 | 15% |
Immunology and Microbiology | 13 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
Other | 8 | 5% |
Unknown | 27 | 16% |