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Replication of recently identified systemic lupus erythematosus genetic associations: a case–control study

Marian Suarez-Gestal1, Manuel Calaza1, Emöke Endreffy2, Rudolf Pullmann3, Josep Ordi-Ros4, Gian Domenico Sebastiani5, Sarka Ruzickova6, Maria Jose Santos78, Chryssa Papasteriades9, Maurizio Marchini10, Fotini N Skopouli11, Ana Suarez12, Francisco J Blanco13, Sandra D'Alfonso14, Marc Bijl15, Patricia Carreira16, Torsten Witte17, Sergio Migliaresi18, Juan J Gomez-Reino119, Antonio Gonzalez1* and the European Consortium of SLE DNA Collections

Author Affiliations

1 Laboratorio de Investigacion 10 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela 15706, Spain

2 Paediatrics Department, Albert Szent-Györgyi Medical and Pharmaceutical Centre, University of Szeged, Szeged 6721, Hungary

3 Institute of Clinical Biochemistry, Martin Faculty Hospital, Jessenius Medical Faculty, Kollárova 2, 036 59 Martin, Slovakia

4 Internal Medicine, Research Laboratory in Autoimmune Diseases, Hospital Vall d'Hebron, 08035 Barcelona, Spain

5 Ospedale S Camillo-Forlanini, U O Complessa di Reumatologia, 00151 Roma, Italy

6 Molecular Biology and Immunogenetics Department, Institute of Rheumatology, 128 50 Prague 2, Czech Republic

7 Rheumatology Department, Hospital Garcia de Orta, Almada, Portugal

8 Rheumatology Research Unit, Instituto Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal

9 Department of Histocompatibility and Immunology, Evangelismos Hospital, 10676 Athens, Greece

10 Clinical Immunology, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milan, Italy

11 Pathophysiology Department, Athens University Medical School, Athens 115 27, Greece

12 Department of Functional Biology, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo 33006, Spain

13 INIBIC-CH Universitario A Coruña, 15006 A Coruña, Spain

14 Dept Medical Sciences and IRCAD, Eastern Piedmont University, 28100 Novara, Italy

15 Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, 9713 Groningen, The Netherlands

16 Rheumatology Unit Hospital 12 de Octubre, 28041 Madrid, Spain

17 Division of Clinical Immunology, Department of Internal Medicine of the Hannover Medical School, D-30625 Hannover, Germany

18 Rheumatology Unit, Second University of Naples, 81100 Naples, Italy

19 Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, 15706, Spain

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Arthritis Research & Therapy 2009, 11:R69  doi:10.1186/ar2698

See related editorial by Cunninghame Graham,

Published: 14 May 2009



We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.


We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel–Haenszel approach to account for heterogeneity between sample collections.


A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.


Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.