- Erratum in:
- Nat Genet. 2008 Apr;40(4):484. Barrizzone, Nadia [corrected to Barizzone, Nadia].
- Comment in:
-
Nat Genet. 2008 Feb;40(2):131-2.
Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus.
Kozyrev SV,
Abelson AK,
Wojcik J,
Zaghlool A,
Linga Reddy MV,
Sanchez E,
Gunnarsson I,
Svenungsson E,
Sturfelt G,
Jönsen A,
Truedsson L,
Pons-Estel BA,
Witte T,
D'Alfonso S,
Barizzone N,
Danieli MG,
Gutierrez C,
Suarez A,
Junker P,
Laustrup H,
González-Escribano MF,
Martin J,
Abderrahim H,
Alarcón-Riquelme ME.
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden.
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.
PMID: 18204447 [PubMed - indexed for MEDLINE]