Background The 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).
Objectives To 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.
Methods Previously 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).
Results Previously described risk alleles from HLA, IRF5, BLK, ITGAM, and IRF8 loci have been identified (P value <0.05). In addition, several genes appear to be related with the different analized subphenotypes. Four of them could be highlighted due to their strongest P value: the risk effect of SNP rs5754217 (UBE2L3) for skin involvement (P value =0.0004), that of rs907715 (IL21) and rs3093030 (ICAM1-ICAM4-ICAM5) for haematological disorders (P value =0.0031 and P value =0.0010, respectively), and rs4240671 (XKR6) for CNS involvement (P value =0.0085).
Conclusions Overall, results from GAPAID project are consistent with previously established associations for HLA, IRF5, BLK, ITGAM, and IRF8 SLE susceptibility loci and report for the first time several subphenotype-specific associations.
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Disclosure of Interest None declared