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Genetic associations of LYN with systemic lupus erythematosus

Genes & Immunity volume 10, pages 397–403 (2009)Cite this article

A Corrigendum to this article was published on 20 January 2010

Abstract

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case–control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 × 10−4, odds ratio (OR)=0.81 (95% confidence interval: 0.73–0.90)). This single nucleotide polymorphism (SNP) is located in the 5′ untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 × 10−3, OR=0.75 (95% CI: 0.62−0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.

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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 (http://lupus.omrf.org), PROFILE, BIOLUPUS and many other individual or multicenter collaborator initiated collections. We also thank the recruitment and technical teams at each of the sample procurement sites for their important contributions. We thank the Wake Forest University Health Sciences Center for Public Health Genomics for support of the data analysis efforts of our Wake Forest University collaborators. Finally, we thank the various funding sources as outlined on the title page for their continued support for the collection of samples and the conduct of this research.

Members of BIOLUPUS who have provided samples to this study are: Peter Junker, Ann Voss and Helle Laustrup (Odense, Denmark), Bernard Lawerys and Fredric Houssieau (Louvain, Belgium), Carlos Vasconcelos and Berta Martins Da Silva (Porto, Portugal), Carmen Gutierrez and Ana Suárez (Oviedo, Spain), Torsten Witte (Hannover, Germany), Sandra D'Alfonso, Sergio Migliaresi, Mauro Galeazzi and Gian Domenico Sebastiani (Novara, Naples, Siena and Rome, Italy), Bernardo Pons-Estel and the members of GENLES (Rosario, Argentina) and Emoke Endreffy (Szeged, Hungary). Peter K Gregersen from the Feinstein Institute of Medical Research and Jorge R Oksenberg from the University of California at San Francisco graciously provided controls used in this study. Members of PROFILE who have provided samples to this study are Graciela S Alarcón, Elizabeth E Brown, Robert P Kimberly, Jeffery C Edberg and Gerald McGwin, Jr (University of Alabama Birmingham, Birmingham, AL, USA), Rosalind Ramsey-Goldman (Northwestern University Feinberg School of Medicine, Chicago, IL, USA), John D Reveille (University Texas Health Science Center, Houston, TX, USA), Luis M Vilá (University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA) and Michelle A Petri (Johns Hopkins Hospital, Baltimore, MD, USA). This project was funded by National Institutes of Health RR020143 (JMG and JBH), RR015577 (JMG, JBH, JAJ), NIAID-HHSN266200500026C (JMG and JAJ), AI031584 (JBH, JMG, JAJ), AR053483 (JMG, SKN and JAJ), AR48940 (JBH, JAJ), AI063622 (SKN), Kirkland Scholar awards (JBH and JAJ), AR049084 (SKN, JBH, RPK, RRG, JDR, MAP, LMV, GSA, JCE, GMcG Jr), AR42460 (JBH), AR12253 (JBH), AR62277 (JBH), AI24717 (JBH), AI063274 (PMG), AR052125 (PMG), AR043247 (KLM), DEO15223 (JBH), Alliance for Lupus Research (JBH), the US Department of Veterans Affairs (JBH), Swedish Research Council (MEAR), the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea. (A010252, A080588) (SCB), the Torsten & Ragnar Söderbergs Foundation (MEAR), the Swedish Foundation Against Rheumatism (MEAR), the Gustaf Vth-80th-Year Foundation (MEAR), Plan Nacional de I+D, Spain (SAF06-00398) (JM), the Junta de Andalucía, grupo CTS-180 (JM) and OHRS award # HR08-037 from the Oklahoma Center for the Advancement of Science & 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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Author notes

  1. R Lu and G S Vidal: These authors contributed equally to this work.

Authors and Affiliations

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

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

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

    J A Kelly, X K Howard, C Burrell, I T Harley, K M Kaufman, G R Bruner, K L Moser, P M Gaffney, J B Harley, M E Alarcón-Riquelme & S K Nath

  3. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

    A M Delgado-Vega & M E Alarcón-Riquelme

  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, Medical Center Blvd, Winston-Salem, NC, USA

    C D Langefeld, M C Marion & 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, Division of Rheumatology and Clinical Immunogenetics, 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, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M A Petri

  13. Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea

    S-C Bae, S-K Cho, S-Y Bang, I Kim & C-B Choi

  14. Instituto de Biomedicina y Parasitología López-Neyra, CSIC, Granada, Spain

    J Martin

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

    T J Vyse

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

    J T Merrill

  17. Departments of Medicine and Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA

    J B Harley & J A James

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  1. R Lu
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  2. G S Vidal
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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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Lu, R., Vidal, G., Kelly, J. et al. Genetic associations of LYN with systemic lupus erythematosus. Genes Immun 10, 397–403 (2009). https://doi.org/10.1038/gene.2009.19

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