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

PurposeTo 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.DesignTwo-stage case-control and functional studies.ParticipantsA total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled.MethodsTaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay.Main Outcome MeasuresAssociation of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs.ResultsIncreased 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).ConclusionsHigh 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.