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

In English

Författare

  • 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 Laustrup
  • Maria Francisca Gonzalez-Escribano
  • Javier Martin
  • Hadi Abderrahim
  • Marta E Alarcon-Riquelme
Visa allt

Summary, in English

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.

Publiceringsår

2008

Språk

Engelska

Sidor

211-216

Publikation/Tidskrift/Serie

Nature Genetics

Volym

40

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

Nature Publishing Group

Ämne

  • Immunology in the medical area
  • Rheumatology and Autoimmunity
  • Microbiology in the medical area

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1546-1718