Association of rs2294020 in the X-linked CCDC22 with susceptibility to autoimmune diseases with focus on systemic lupus erythematosus

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-kB, 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. Corresponding author: Fabio D'Amico, Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, I-95124 Catania, Italy. f.damico@unict.it. 1Contributed equally †Deceased in July 2016 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Immunol Lett. Author manuscript; available in PMC 2018 January 01. Published in final edited form as: Immunol Lett. 2017 January ; 181: 58–62. doi:10.1016/j.imlet.2016.11.011. A uhor M anscript