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The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis

Genes & Immunity volume 11, pages 439–445 (2010)Cite this article

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Abstract

Genome-wide association studies (GWAS) have revealed that different diseases share susceptibility variants. Twelve single-nucleotide polymorphisms (SNPs) previously associated with different immune-mediated diseases in GWAS were genotyped in a Caucasian Spanish population of 2864 multiple sclerosis (MS) patients and 2930 controls. Three SNPs were found to be associated with MS: rs1678542 in KIF5A (P=0.001, odds ratio (OR)=1.13, 95% confidence interval (CI)=1.05–1.23); rs3184504 in SH2B3 (P=0.00001, OR=1.19, 95% CI=1.10–1.27) and rs763361 in CD226 (P=0.00007, OR=1.16, 95%CI=1.08–1.25). These variants have previously been associated with rheumatoid arthritis and type 1 diabetes. The SH2B3 polymorphism has additionally been associated with systemic lupus erythematosus. Our results, in addition to validating some of these loci as risk factors for MS, are consistent with shared genetic mechanisms underlying different immune-mediated diseases. These data may help to shape the contribution of each pathway to different disorders.

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Acknowledgements

We thank the patients with multiple sclerosis and persons who acted as controls for making this study possible. Financial support for the study was provided by Fondos Europeos de Desarrollo Regional (FEDER), Ministerio de Ciencia e Innovación (SAF2006-02023 and SAF2009-11491), Junta de Andalucía (P07-CVI-02551), Fondo de Investigación Sanitaria (RETICS-REEM RD07/0060, PI081636, PI070353, PS0902105), Ikerbasque, Basque Foundation for Science, Bilbao and Fundación ILUNDAIN. Genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado’ CEGEN-USC (www.cegen.org).

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Author notes

  1. A Alcina, K Vandenbroeck, D Otaegui, A Saiz, E Urcelay and F Matesanz: These authors contributed equally to this work.

Authors and Affiliations

  1. Instituto de Parasitología y Biomedicina ‘López Neyra’, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain

    A Alcina, M Fedetz & F Matesanz

  2. Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain

    K Vandenbroeck & I Alloza

  3. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

    K Vandenbroeck

  4. Área de Neurociencias, Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain

    D Otaegui

  5. Neurology Service, Hospital Clinic and Institut d’Investigació Biomèdica Pi i Sunyer (IDIBAPS), Barcelona, Spain

    A Saiz & Y Blanco

  6. Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBERESP, Institut Municipal d’Investigació Mèdica (IMIM), Barcelona, Spain

    J R Gonzalez

  7. Servicio de Neurología and Instituto de Neurociencias Clínicas del Hospital Regional Universitario Carlos Haya, Málaga, Spain

    O Fernandez

  8. Immunology and Neurology Department, Hospital Clínico S. Carlos, Madrid, Spain

    M L Cavanillas, M C Cénit, R Arroyo & E Urcelay

  9. Servicio de Genética, Hospital de Basurto, Bilbao, Spain

    M García-Barcina

  10. Servicio de Neurología, Hospital de Basurto, Bilbao, Spain

    A Antigüedad

  11. Laboratorio de Investigación, Instituto de Neurociencias Clínicas del Hospital Regional Universitario Carlos Haya, Málaga, Spain

    L Leyva & M J Pinto-Medel

  12. Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain

    G Izquierdo

  13. Servicio de Biología Molecular, Hospital Virgen Macarena, Sevilla, Spain

    M Lucas

  14. Servicio de Neurología, Unidad de esclerosis múltiple, Hospital Donostia, San Sebastián, Spain

    J Olascoaga

  15. Centre d’Esclerosi Múltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    M Comabella & X Montalban

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  1. A Alcina
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  15. M Lucas
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Correspondence to F Matesanz.

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Alcina, A., Vandenbroeck, K., Otaegui, D. et al. The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis. Genes Immun 11, 439–445 (2010). https://doi.org/10.1038/gene.2010.30

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  • DOI: https://doi.org/10.1038/gene.2010.30

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