Abstract
PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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Acknowledgements
We thank the Swedish Research Council, the Swedish Association Against Rheumatism, the Gustav V:e 80-års foundation, the Marcus Borgströms Foundation, the Magnus Bergvalls Foundation and the Alliance for Lupus Research (USA) for financial support to MEAR, and the Gustaf Prim Foundation for support to AKA. We also thank Juni Palmgren at the University of Stockholm for valuable comments regarding the statistics and the CEDIM, Diagnóstico Molecular y Forense SRL. Rosario, Argentina for DNA preparation of some samples used here. MEAR is a recipient of a research fellowship from the Royal Swedish Academy of Sciences financed by the Knut and Alice Wallenberg Foundation.
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The Argentine Collaborative group is composed of the following members: Pilar C Marino, MD, Estela L Motta, MD Servicio de Reumatología, Hospital Interzonal General de Agudos ‘Dr Oscar Alende’, Mar del Plata, Argentina; Cristina Drenkard, MD, Emilia Menso, MD Servicio de Reumatología de la UHMI 1, Hospital Nacional de Clínicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Guillermo A Tate, MD Organización Médica de Investigación, Buenos Aires, Argentina; Jose L Presas, MD Hospital General de Agudos Dr Juán A Fernandez, Buenos Aires, Argentina; Marcelo Abdala, MD, Mariela Bearzotti, PhD Facultad de Ciencias Medicas, Universidad Nacional de Rosario y Hospital Provincial del Centenario, Rosario, Argentina; Francisco Caeiro, MD, Ana Bertoli, MD Servicio de Reumatología, Hospital Privado, Centro Medico de Córdoba, Córdoba, Argentina; Susana Roverano, MD, Hospital José M Cullen, Santa Fe, Argentina; Cesar E Graf, MD (*) Griselda Buchanan, PhD (**), Estela Bertero, PhD (*), (*) Hospital San Martín, Paraná, (**) Hospital Felipe Heras, Concordia, Entre Ríos, Argentina; Sebastian Grimaudo, PhD, Jorge Manni, MD Departamento de Inmunología, Instituto de Investigaciones Médicas ‘Alfredo Lanari’, Buenos Aires, Argentina; Enrique R Soriano, MD, Carlos D Santos, MD Sección Reumatología, Servicio de Clínica Medica, Hospital Italiano de Buenos Aires y Fundación Dr Pedro M Catoggio para el Progreso de la Reumatología, Buenos Aires, Argentina; Fernando A Ramos, MD, Sandra M Navarro, MD Servicio de Reumatología, Hospital Provincial de Rosario, Rosario, Argentina; Marisa Jorfen, MD, Elisa J Romero, PhD Servicio de Reumatología Hospital Escuela Eva Perón, Granadero Baigorria, Rosario, Argentina; Juan C Marcos, MD, Ana I Marcos, MD Servicio de Reumatología, Hospital Interzonal General de Agudos General San Martín, La Plata, Argentina; Alicia Eimon, MD Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina.
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Abelson, A., Johansson, C., Kozyrev, S. et al. No evidence of association between genetic variants of the PDCD1 ligands and SLE. Genes Immun 8, 69–74 (2007). https://doi.org/10.1038/sj.gene.6364360
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DOI: https://doi.org/10.1038/sj.gene.6364360
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