title: Genetic association study of systemic lupus erythematosus and disease subphenotypes in European populations.
abstract: Epidemiological studies suggest a strong contribution of genetic factors in the pathogenesis of systemic lupus erythematosus (SLE). In the last decades, many risk loci have been identified in several genetic association studies following both candidate gene and genome-wide approaches. The present work was conducted by GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium with a dual aim: to replicate the association of several previously reported SLE susceptibility loci in an independent European sample and to explore their relation with some disease subphenotypes. A total of 48 single nucleotide polymorphisms (SNP) from 40 associated loci were typed in a cohort of 208 SLE patients and 152 controls from Rheumatology Units of the University Hospital of Pisa (Italy) and University of Pécs Medical Center (Hungary). Regression analyses were performed to detect disease susceptibility loci and to identify genes affecting specific disease manifestations (renal, neurological, or skin involvement; arthritis; secondary Sjögren syndrome; and secondary antiphospholipid syndrome). Association of previously described risk alleles from HLA locus has been replicated, while IRF5, BLK, ITGAM, and IRF8 loci have been found to be consistent with previous published results. In addition, two new subphenotype-specific associations have been detected: SNP rs5754217 (UBE2L3) with skin involvement and rs3093030 (ICAM1-ICAM4-ICAM5) with hematological disorders. 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 two subphenotype-specific associations.
authors.affiliation: Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country (UPV/EHU), Leioa, Spain. otsanda.ruiz@ehu.eus.
authors.forename: Otsanda
authors.initials: O
authors.lastname: Ruiz-Larrañaga
authors.affiliation: Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.affiliation: Department of Research and Development, Progenika Biopharma S.A., Derio, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Uribarri
authors.affiliation: Department of Rheumatology and Immunology, University of Pécs, Pécs, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Czirják
authors.affiliation: Department of Research and Development, Toscana Biomarkers S.r.l., Siena, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Alcaro
authors.affiliation: Department of Research and Development, Progenika Biopharma S.A., Derio, Spain.
authors.forename: Jokin
authors.initials: J
authors.lastname: Del Amo
authors.affiliation: Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Mikel
authors.initials: M
authors.lastname: Iriondo
authors.affiliation: Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Manzano
authors.affiliation: Department of Research and Development, Progenika Biopharma S.A., Derio, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Escorza-Treviño
authors.affiliation: Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Andone
authors.initials: A
authors.lastname: Estonba
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
keywords: Clinical manifestations; Genetics; Single nucleotide polymorphism; Systemic lupus