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Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population

Genes & Immunity volume 10, pages 531–538 (2009)Cite this article

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype–phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value=1.97 × 10−5, odds ratio (OR)=1.22, 95% CI 1.12–1.34) and rs10516487 (corrected P-value=2.59 × 10−5, OR=1.22, 95% CI 1.11–1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.

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Acknowledgements

We thank the participants, both patients and controls, who graciously agreed to take part in these studies by donating samples to the various collections, including the Lupus Family Registry and Repository (LFRR: http://lupus.omrf.org), PROFILE, BIOLUPUS, Feinstein Institute for Medical Research and many other individual or multicenter collaborators. We also thank the recruitment and technical teams at each of the sample procurement sites for their important contributions. We acknowledge the Wake Forest University Health Sciences Center for Public Health Genomics for support of the data analysis efforts by our Wake Forest University collaborators. We thank Dr Alarcon-Riquelme for her assistance in clearly identifying potential overlapping subjects between our collections to ensure the independence of this study's observed associations and Dr Peter Gregersen for providing control samples. Finally, we acknowledge the various funding sources as mentioned below for their continued support for the collection of samples and the conduct of this research.

Support: This project was funded by National Institutes of Health RR020143 (JMG and JBH), RR015577 (JMG, JBH, JAJ), HHSN266200500026C (JMG and JAJ), AR053483 (JMG, SKN and JAJ), AI063274 (PMG), AI031584 (JBH, JMG, JAJ), AR052125 (PMG), AR043247 (KLM), Kirkland Scholar awards (JBH and JAJ), AR049084 (SKN, JBH, RPK), AR42460 (JBH), AR12253 (JBH), AR62277 (JBH), AI24717 (JBH), AR48940 (JBH, JAJ), Alliance for Lupus Research (JBH), the US Department of Veterans Affairs (JBH) and OHRS award for project number HR08-037 from the Oklahoma Center for the Advancement of Science and Technology (JMG). Dr Harley has received consulting fees, speaking fees and/or director's fees from Bio-Rad Laboratories; Merck; UCB Inc.; ImmunoVision Inc.; IVAX Diagnostics and JK Autoimmunity and owns stock or stock options in IVAX Diagnostics.

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Authors and Affiliations

  1. Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    L Guo, H Deshmukh, J A Kelly, K M Kaufman, X Kim-Howard, G R Bruner, R H Scofield, K L Moser, P M Gaffney, I M Dozmorov, S K Nath & J B Harley

  2. Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA

    L Guo, J A James & J B Harley

  3. Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    R Lu, G S Vidal, N Dominguez, W Klein, J A James & J M Guthridge

  4. US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

    K M Kaufman & J B Harley

  5. Division of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA

    G S Gilkeson

  6. Department of Immunology, University of Texas at Southwest Medical Center, Dallas, TX, USA

    E K Wakeland & Q-Z Li

  7. Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    C D Langefeld, M C Marion, A H Williams & J Divers

  8. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    G S Alarcón, E E Brown, R P Kimberly, J C Edberg & G McGwin Jr

  9. Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    R Ramsey-Goldman

  10. Department of Internal Medicine, University of Texas-Houston Health Sciences Center, Houston, TX, USA

    J D Reveille

  11. Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

    L M Vilá

  12. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M A Petri

  13. Rheumatology Section, Imperial College, Hammersmith Hospital, London, UK

    T J Vyse

  14. Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    J T Merrill

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  1. L Guo
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  2. H Deshmukh
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  3. R Lu
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  4. G S Vidal
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  5. J A Kelly
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  16. E K Wakeland
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  17. Q-Z Li
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  18. C D Langefeld
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  21. J Divers
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  22. G S Alarcón
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  27. J D Reveille
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  28. G McGwin Jr
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  29. L M Vilá
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  33. J A James
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  34. S K Nath
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  35. J B Harley
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Corresponding author

Correspondence to J M Guthridge.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Guo, L., Deshmukh, H., Lu, R. et al. Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population. Genes Immun 10, 531–538 (2009). https://doi.org/10.1038/gene.2009.18

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