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Genetic association study of systemic lupus erythematosus and disease subphenotypes in European populations

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Abstract

Epidemiological studies suggest a strong contribution of genetic factors in the pathogenesis of systemic lupus erythematosus (SLE). In the last decades, many risk loci have been identified in several genetic association studies following both candidate gene and genome-wide approaches. The present work was conducted by GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium with a dual aim: to replicate the association of several previously reported SLE susceptibility loci in an independent European sample and to explore their relation with some disease subphenotypes. A total of 48 single nucleotide polymorphisms (SNP) from 40 associated loci were typed in a cohort of 208 SLE patients and 152 controls from Rheumatology Units of the University Hospital of Pisa (Italy) and University of Pécs Medical Center (Hungary). Regression analyses were performed to detect disease susceptibility loci and to identify genes affecting specific disease manifestations (renal, neurological, or skin involvement; arthritis; secondary Sjögren syndrome; and secondary antiphospholipid syndrome). Association of previously described risk alleles from HLA locus has been replicated, while IRF5, BLK, ITGAM, and IRF8 loci have been found to be consistent with previous published results. In addition, two new subphenotype-specific associations have been detected: SNP rs5754217 (UBE2L3) with skin involvement and rs3093030 (ICAM1-ICAM4-ICAM5) with hematological disorders. Overall, results from GAPAID project are consistent with previously established associations for HLA, IRF5, BLK, ITGAM, and IRF8 SLE susceptibility loci and report for the first time two subphenotype-specific associations.

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Acknowledgments

The authors thank for the technical and human support provided by Sequencing and Genotyping Facilities from SGIker of UPV/EHU. This work was supported by the European Union Seventh Framework Programme FP7/2007-2013 (grant agreement n° 314971).

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Authors and Affiliations

  1. Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country (UPV/EHU), Leioa, Spain

    Otsanda Ruiz-Larrañaga, Mikel Iriondo, Carmen Manzano & Andone Estonba

  2. Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Paola Migliorini

  3. Department of Research and Development, Progenika Biopharma S.A., Derio, Spain

    Maria Uribarri, Jokin del Amo & Sergio Escorza-Treviño

  4. Department of Rheumatology and Immunology, University of Pécs, Pécs, Hungary

    László Czirják

  5. Department of Research and Development, Toscana Biomarkers S.r.l., Siena, Italy

    Maria C Alcaro

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  1. Otsanda Ruiz-Larrañaga
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  2. Paola Migliorini
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  3. Maria Uribarri
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  4. László Czirják
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  5. Maria C Alcaro
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  6. Jokin del Amo
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  7. Mikel Iriondo
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  8. Carmen Manzano
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  9. Sergio Escorza-Treviño
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  10. Andone Estonba
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Correspondence to Otsanda Ruiz-Larrañaga.

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Ethic statement

This study was approved by the Ethics Committee of the University Hospital of Pisa (reference number: 45066/2012) and the Hungarian Scientific and Research Ethics Board (reference number: 24973-1/2012 EKU). The procedures followed were in accordance with the Helsinki Declaration of 1975. All the patients gave written informed consent.

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Ruiz-Larrañaga, O., Migliorini, P., Uribarri, M. et al. Genetic association study of systemic lupus erythematosus and disease subphenotypes in European populations. Clin Rheumatol 35, 1161–1168 (2016). https://doi.org/10.1007/s10067-016-3235-8

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  • DOI: https://doi.org/10.1007/s10067-016-3235-8

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