title: Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases with focus on systemic lupus erythematosus.
abstract: Autoimmune diseases often share common susceptibility genes. Most genetic variants associated with susceptibility to systemic lupus erythematosus are also associated with other autoimmune diseases. The X-linked variant rs2294020 is positioned in exon 7 of the CCDC22 gene. The encoded protein functions in the regulation of NF-κB, a master regulator in immune response. The aim of this study is to investigate whether the rs2294020 polymorphism may be a general susceptibility factor for autoimmunity. We evaluated case-control association between the occurrence of rs2294020 and different autoimmune diseases, including new data for systemic lupus erythematosus and previous genome-wide association studies (GWAS) (though most did not analyse the X chromosome) of psoriasis, celiac disease, Crohn's disease, ulcerative colitis, multiple sclerosis, vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis. Cases from patients affected by amyotrophic lateral sclerosis and type-2 diabetes were also included in the study. We detected nominal significant associations of rs2294020 with systemic lupus erythematosus (additive model test: p=0.01), vitiligo (p=0.016), psoriasis (p=0.038), and in only one of two studies of multiple sclerosis (p=0.03). Our results suggest that rs2294020 is associated with the risk of several autoimmune diseases in European populations, specifically with diseases that present themselves, among else, in the skin.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Androne 83, I-95124 Catania, Italy. Electronic address: f.damico@unict.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: D'Amico
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Androne 83, I-95124 Catania, Italy.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Skarmoutsou
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Lo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Androne 83, I-95124 Catania, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Granata
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Androne 83, I-95124 Catania, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Trovato
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Androne 83, I-95124 Catania, Italy.
authors.forename: Giulio A
authors.initials: GA
authors.lastname: Rossi
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Pace 9, I-20122 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellocchi
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Pace 9, I-20122 Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marchini
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Pace 9, I-20122 Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Androne 83, I-95124 Catania, Italy.
authors.forename: Maria Clorinda
authors.initials: MC
authors.lastname: Mazzarino
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Alon
authors.initials: A
authors.lastname: Keinan
mesh_terms: D000328:Adult; D000483:Alleles; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D050172:Genes, X-Linked; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: C571908:CCDC22 protein, human; D011506:Proteins
keywords: Autoimmune disease; CCDC22 gene; FOXP3 gene; Single nucleotide polymorphism; Systemic lupus erythematosus