Association of interleukin 23 receptor gene with sarcoidosis

Article type: Research Article

Authors: Kim, Hyun Soo | Choi, Dongseok | Lim, Lyndell L. | Allada, Gopal | Smith, Justine R. | Austin, Carrie R. | Doyle, Trudy M. | Goodwin, Kelley A. | Rosenbaum, James T. | Martin, Tammy M.

Affiliations: Department of Laboratory Medicine, Hallym University College of Medicine, Seoul, Korea | Division of Biostatistics, Department of Public Health & Preventive Medicine, Oregon Health & Science University, Portland, OR, USA | Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia | Pulmonology and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA | Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA

Note: [] Corresponding author: Tammy M. Martin, Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science, University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Tel.: +1 503 494 3372; Fax: +1 503 494 6875; E-mail: martint@ohsu.edu

Abstract: Interleukin 23 receptor (IL23R) gene has been reported as a genetic factor strongly associated with inflammatory bowel disease, psoriasis, and ankylosing spondylitis. We investigated the association between IL23R gene single nucleotide polymorphisms (SNPs) and susceptibility to sarcoidosis, including the clinical manifestation of uveitis. Ninety-one sarcoidosis subjects (58 with and 33 without uveitis) and 104 healthy controls were genotyped for eleven IL23R SNPs. DNA was amplified using specific PCR primers and genotyped by denaturing HPLC and/or direct DNA sequencing. Case-control frequency comparisons were analyzed using Chi square test. Three IL23R SNPs, rs7517847 (intron 6), rs11465804 (intron 8), and rs11209026 (exon 9, c.1142G>A, p.Arg381Gln) were associated with sarcoidosis in our population (p<0.05): rs7517847 showed increased frequencies in sarcoidosis compared to controls, but rs11465804 and rs11209026 were decreased. Two of these SNPs were associated with the uveitis subgroup compared to controls: rs11465804 (0.9% vs. 7.2%, OR=0.11, P=0.013) and rs11209026 (1.8% vs. 7.3%, OR=0.23, P=0.038). This finding indicates the association of IL23R polymorphism with sarcoidosis, especially with sarcoid uveitis. IL23R may be a common susceptibility gene shared by several autoimmune disorders including inflammatory bowel disease, psoriasis, and ankylosing spondylitis and sarcoid uveitis.

Keywords: Interleukin 23 receptor, polymorphism, sarcoidosis, uveitis

DOI: 10.3233/DMA-2011-0796

Journal: Disease Markers, vol. 31, no. 1, pp. 17-24, 2011