AB0016 Retrospective Cohort Study of Systemic Lupus Erythematosus and Disease Subphenotypes in European Populations: Results from Gapaid Project

BackgroundThe GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium was created within the European Union's Seventh Framework Programme for Research and Technological Development (FP7), with the aim of validating gene and protein biomarkers for autoimmune diseases such as systemic lupus erythematosus (SLE). This is an autoimmune disease characterized by a loss of tolerance to self-antigens, inflammation and dysregulated immune responses leading to multi-organ damage and affecting predominantly women (1). The wide spectrum of clinical manifestations shown by the disease complicates its diagnosis, treatment and research (2). Epidemiological studies suggest strong contribution of genetic factors in the pathogenesis of the disease and many SLE risk loci have been identified in several genome-wide association studies (GWAS) and other association studies in the last decades (3).ObjectivesTo perform a replication study for several previously reported SLE susceptibility loci in an independent European sample and to assess their specificity with the different subphenotypes of the disease.MethodsPreviously associated 49 single nucleotide polymorphisms (SNP) were typed in a cohort of 208 SLE patients and 152 controls from Rheumatology Units of University Hospital of Pisa (Italy) and University of Pécs Medical Center (Hungary). Regression analyses were performed focused on the confirmation of disease susceptibility loci and identification of specific genes for age onset, renal, neurological and skin involvement, and presence of arthritis, secondary Sjögren syndrome and secondary antiphospholipid syndrome (APS).ResultsPreviously described risk alleles from HLA, IRF5, BLK, ITGAM, and IRF8 loci have been identified (P value