Functional Variants in the B-Cell Gene BANK1 are Associated with Systemic Lupus Erythematosus
2008 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 40, no 2, 211-216 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 40, no 2, 211-216 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-97762DOI: 10.1038/ng.79ISI: 000252732900020OAI: oai:DiVA.org:uu-97762DiVA: diva2:172822