Shengping Hou1, Dan Liao2, Jun Zhang2, Jing Fang2, Lu Chen2, Jian Qi2, Qi Zhang2, Yunjia Liu2, Lin Bai2, Yan Zhou2, Aize Kijlstra3, Peizeng Yang4. 1. Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China. Electronic address: sphou828@163.com. 2. Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China. 3. University Eye Clinic Maastricht, Maastricht, the Netherlands. 4. Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China. Electronic address: peizengycmu@126.com.
Abstract
PURPOSE: To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) and the possible mechanisms involved. DESIGN: Two-stage case-control and functional studies. PARTICIPANTS: A total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled. METHODS: TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay. MAIN OUTCOME MEASURES: Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs. RESULTS: Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P=4.17×10(-8); odds ratio [OR], 2.2; IL23A: P=2.86×10(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P=2.84×10(-13); OR, 2.7; IL23A: P=4.46×10(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P=1.06×10(-6); OR, 2.3; IL23A, P=3.81×10(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P=3.43×10(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P=5.67×10(-3)). CONCLUSIONS: High gene copy numbers of IL17F and IL23A were associated with BD and VKH syndrome. Enhanced IL17F protein production and PBMC proliferation were associated with high IL17F copy numbers.
PURPOSE: To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) and the possible mechanisms involved. DESIGN: Two-stage case-control and functional studies. PARTICIPANTS: A total of 1159 VKHpatients, 1036 BD patients, and 2050 controls were enrolled. METHODS: TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay. MAIN OUTCOME MEASURES: Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs. RESULTS: Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P=4.17×10(-8); odds ratio [OR], 2.2; IL23A: P=2.86×10(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P=2.84×10(-13); OR, 2.7; IL23A: P=4.46×10(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P=1.06×10(-6); OR, 2.3; IL23A, P=3.81×10(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P=3.43×10(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P=5.67×10(-3)). CONCLUSIONS: High gene copy numbers of IL17F and IL23A were associated with BD and VKH syndrome. Enhanced IL17F protein production and PBMC proliferation were associated with high IL17F copy numbers.
Authors: Shengping Hou; Zi Ye; Dan Liao; Lin Bai; Yunjia Liu; Jun Zhang; Aize Kijlstra; Peizeng Yang Journal: Sci Rep Date: 2016-01-28 Impact factor: 4.379