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

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 Barrizzone, Maria Giovanna Danieli, Carmen Gutierrez, Ana Suarez, Peter Junker, Helle LaustrupMaria Francisca González-Escribano, Javier Martin, Hadi Abderrahim, Marta E. Alarcón-Riquelme

Research output: Contribution to journalArticle

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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 × 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 (Δ2), 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.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalNature Genetics
Volume40
Issue number2
DOIs
Publication statusPublished - 1 Feb 2008
Externally publishedYes

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Systemic Lupus Erythematosus
B-Lymphocytes
Single Nucleotide Polymorphism
Ankyrin Repeat
Ankyrins
Genes
Linkage Disequilibrium
Autoantibodies
Autoimmune Diseases
Exons
Protein Isoforms
Proteins
Complementary DNA
Genome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Kozyrev, S. V., Abelson, A. K., Wojcik, J., Zaghlool, A., Linga Reddy, M. V. P., Sanchez, E., ... Alarcón-Riquelme, M. E. (2008). Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nature Genetics, 40(2), 211-216. https://doi.org/10.1038/ng.79

Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. / Kozyrev, Sergey V.; Abelson, Anna Karin; Wojcik, Jerome; Zaghlool, Ammar; Linga Reddy, M. V Prasad; Sanchez, Elena; Gunnarsson, Iva; Svenungsson, Elisabet; Sturfelt, Gunnar; Jönsen, Andreas; Truedsson, Lennart; Pons-Estel, Bernardo A.; Witte, Torsten; D'Alfonso, Sandra; Barrizzone, Nadia; Danieli, Maria Giovanna; Gutierrez, Carmen; Suarez, Ana; Junker, Peter; Laustrup, Helle; González-Escribano, Maria Francisca; Martin, Javier; Abderrahim, Hadi; Alarcón-Riquelme, Marta E.

In: Nature Genetics, Vol. 40, No. 2, 01.02.2008, p. 211-216.

Research output: Contribution to journalArticle

Kozyrev, SV, Abelson, AK, Wojcik, J, Zaghlool, A, Linga Reddy, MVP, Sanchez, E, Gunnarsson, I, Svenungsson, E, Sturfelt, G, Jönsen, A, Truedsson, L, Pons-Estel, BA, Witte, T, D'Alfonso, S, Barrizzone, N, Danieli, MG, Gutierrez, C, Suarez, A, Junker, P, Laustrup, H, González-Escribano, MF, Martin, J, Abderrahim, H & Alarcón-Riquelme, ME 2008, 'Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus', Nature Genetics, vol. 40, no. 2, pp. 211-216. https://doi.org/10.1038/ng.79
Kozyrev SV, Abelson AK, Wojcik J, Zaghlool A, Linga Reddy MVP, Sanchez E et al. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nature Genetics. 2008 Feb 1;40(2):211-216. https://doi.org/10.1038/ng.79
Kozyrev, Sergey V. ; Abelson, Anna Karin ; Wojcik, Jerome ; Zaghlool, Ammar ; Linga Reddy, M. V Prasad ; Sanchez, Elena ; Gunnarsson, Iva ; Svenungsson, Elisabet ; Sturfelt, Gunnar ; Jönsen, Andreas ; Truedsson, Lennart ; Pons-Estel, Bernardo A. ; Witte, Torsten ; D'Alfonso, Sandra ; Barrizzone, Nadia ; Danieli, Maria Giovanna ; Gutierrez, Carmen ; Suarez, Ana ; Junker, Peter ; Laustrup, Helle ; González-Escribano, Maria Francisca ; Martin, Javier ; Abderrahim, Hadi ; Alarcón-Riquelme, Marta E. / Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. In: Nature Genetics. 2008 ; Vol. 40, No. 2. pp. 211-216.
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