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Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against intracellular components, the formation of immune complexes, and inflammation in various organs, typically the skin and kidney glomeruli. The etiology of the disease is not well understood but is most likely the result of the interaction between genetic and environmental factors. In order to identify susceptibility loci for SLE, we have performed genome scans with microsatellite markers covering the whole genome in families from Argentina, Italy, and Europe. The results reveal a heterogeneous disease with different susceptibility loci in different family sets. We have found significant linkage to chromosome 17p12-q11 in the Argentine set of families. The maximum LOD score was given by marker D17S1294 in combination with D17S1293, when assuming a dominant inheritance model (Z=3.88). We also analyzed a repeat in the promoter region of the NOS2A gene, a strong candidate gene in the region, but no association was found. The locus on chromosome 17 has previously been identified in genetic studies of multiple sclerosis families. Several other interesting regions were found at 1p35, 1q31, 3q26, 5p15, 11q23 and 19q13, confirming previously identified loci for SLE or other autoimmune diseases.

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We thank the Uppsala Genome Center (Inger Jonasson, Jenny Jonsson, and Ann-Sofie Strand) for performing all the genotyping, Jenny von Salome for DNA preparation of the Argentine families, and Bo Johanneson for fruitful discussions regarding this manuscript. This project was supported by a grant to C.J. from the “Network for Inflammation Research” funded by the Swedish Foundation for Strategic Research, and grants from the Swedish Research Council, the Swedish Association Against Rheumatism, the Swedish Medical Association, the Clas Groschinsky Memorial Foundation, and the King Gustaf Vth 80-year Jubilee Foundation. M.E.A-R. is partly supported by the Beijer Foundation.

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Correspondence to Marta E. Alarcón-Riquelme.

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A list of members of the Collaborative Group on the Genetics of SLE and the Argentine Collaborative Group is given in the Appendix

Bernardo Pons-Estel is the coordinator of the Argentine Collaborative Group



The collaborative group on the genetics of SLE consists of the following senior researchers: Dr. Kristjan Steinsson (Department of Rheumatology Research, Landspitalinn, Reykjavik, Iceland); Prof. Gunnar Sturfelt (Department of Rheumatology, Lund University, Lund, Sweden); Dr. Iva Gunnarsson and Dr. Elisabet Svennungson (Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden); Dr. Caroline Gordon (Department of Rheumatology, University of Birmingham, United Kingdom); Prof. Roland Jonsson (Broegelmann Research Laboratory, University of Bergen, Bergen, Norway); Prof. Haralampos Moutsopoulos (School of Medicine, Athens University, Greece); Dr. Andrea Doria (University of Padua, Italy).

Other participants from Argentina were: Dr. Juan C. Marcos and Dr. Ana I. Marcos (Servicio de Reumatología, Hospital Interzonal General de Agudos General San Martín, La Plata); Dr. Pilar C. Marino and Dr. Estela L. Motta (Servicio de Reumatología, Hospital Interzonal General de Agudos “Dr. Oscar Alende”, Mar del Plata); Dr. Alberto Allevi and Dr. Jose L. Presas (Hospital General de Agudos Dr. Juán A. Fernandez, Buenos Aires); Dr. Roverano and Dr. Carlos Louteiro (Hospital José M. Cullen, Santa Fe); Dr. Fernando A. Ramos and Dr. Cristina S. Prigione (Servicio de Reumatología, Hospital Provincial de Rosario, Rosario); Dr. Alicia Eimon (Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires); Dr. Cristina Drenkard and Dr. Emilia Menso (Servicio de Reumatología de la UHMI 1, Hospital Nacional de Clínicas, Universidad Nacional de Córdoba, Córdoba); Dr. Francisco Caeiro and Dr. Ana Bertoli (Servicio de Reumatología, Hospital Privado, Centro Medico de Córdoba, Córdoba); Dr. Cesar Caprarulo and Dr. Griselda Buchanan (Hospital Felipe Heras, Concordia); Dr. Estela Bertero (Hospital San Martín, Paraná, Entre Ríos); Dr. Sebastian Grimaudo and Dr. Carolina Guillersn (Departamento de Inmunología, Instituto de Investigaciones Médicas “Alfredo Lanari”, Buenos Aires); Dr. Marisa Jorfen and Dr. Elisa J. Romero (Servicio de Reumatología Hospital Escuela Eva Perón. Granadero Baigorria, Rosario); Dr. Marcelo Abdala and Dr. Mariela Bearzotti (Facultad de Ciencias Medicas, Universidad Nacional de Rosario y Hospital Provincial del Centenario, Rosario); Dr. Enrique R. Soriano and Dr. Carlos D. Santos (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); Dr. Carlos A. Battagliotti (Sanatorio Parque, Rosario).

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Johansson, C.M., Zunec, R., García, M.A. et al. Chromosome 17p12-q11 harbors susceptibility loci for systemic lupus erythematosus. Hum Genet 115, 230–238 (2004).

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