Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study

Elisa Alonso-Perez, Marian Suarez-Gestal, Manuel Calaza, Josep Ordi-Ros, Eva Balada, Marc Bijl, Chryssa Papasteriades, Patricia Carreira, Fotini N. Skopouli, Torsten Witte, Emöke Endreffy, Maurizio Marchini, Sergio Migliaresi, Gian Domenico Sebastiani, Maria Jose Santos, Ana Suarez, Francisco J. Blanco, Nadia Barizzone, Rudolf Pullmann, Sarka RuzickovaBernard R. Lauwerys, Juan J. Gomez-Reino, Antonio Gonzalez, Myriam Liz, Reinhold E. Schmidt, Iris Kappou-Rigatou, Raffaella Scorza, Attila Kovacs, Eva Balada, Cees G. Kallenberg, Filipe Vinagre, Ctibor Dostal, Rudolf Pullmann, Maria Mavromati, Sandra D'Alfonso, Carmen Gutierrez, Ignacio Rego

Research output: Contribution to journalArticlepeer-review


Introduction: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. Methods: European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. Results: There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, Pcorr = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. Conclusion: Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component.

Original languageEnglish
Article numbere45356
JournalPLoS One
Issue number9
Publication statusPublished - Sep 26 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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