Genetic Variations of IL17F and IL23A Show Associations with Behçet’s Disease and Vogt-Koyanagi-Harada Syndrome

Purpose To investigate the associations of IL17A , IL17F , IL23A , and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet'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.