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.
journal_name
Ophthalmologyjournal_title
Ophthalmologyauthors
Hou S,Liao D,Zhang J,Fang J,Chen L,Qi J,Zhang Q,Liu Y,Bai L,Zhou Y,Kijlstra A,Yang Pdoi
10.1016/j.ophtha.2014.09.025subject
Has Abstractpub_date
2015-03-01 00:00:00pages
518-23issue
3eissn
0161-6420issn
1549-4713pii
S0161-6420(14)00903-8journal_volume
122pub_type
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