PURPOSE: The purpose of this study was to test whether gene copy number 
variations (CNVs) of Toll-like receptors (TLRs) are associated with uveitis.
METHODS: Copy number variations of TLRs were detected by real-time PCR. The 
first stage of the study consisted of enrolling 400 Behçet's disease (BD) 
patients, 400 Vogt-Koyanagi-Harada syndrome patients, 400 patients with acute 
anterior uveitis associated with or without ankylosing spondylitis, and 600 
healthy subjects. The second stage included another set of 578 BD patients and 
1000 healthy controls. The frequencies of TLR gene copy number types (TLR1, 
TLR2, TLR3, TLR5, TLR6, TLR7, TLR9, TLR10) were compared among patients and 
controls by using the χ(2) test. Real-time PCR was used to detect mRNA 
expression from peripheral blood mononuclear cells (PBMCs) obtained from healthy 
controls following stimulation with the TLR7 agonist R848. Levels of TNF-α, 
IL-6, IL-1β, and IFN-β in culture supernatants were measured by ELISA.
RESULTS: All TLRs tested, except for TLR7, had a gene copy number of two in more 
than 98% of individuals tested. In the first stage, we found a significantly 
increased frequency of more than one copy of TLR7 (located on the X chromosome) 
in male BD patients and more than two copies in female patients (correction of P 
value [PC] = 0.021; PC = 0.048, respectively). A second stage and combined study 
confirmed the association (PC = 1.14 × 10(-6); PC = 9.12 × 10(-5), 
respectively). TLR7 mRNA expression in PBMCs was increased in healthy male 
carriers having more than one copy of TLR7 or females having more than two 
copies following stimulation with R848 (P = 0.021, P = 0.006, respectively). No 
effect of the various TLR7 copies on the release of TNF-α, IL-6, IL-1β, and 
IFN-β could be detected.
CONCLUSIONS: This study provides evidence that a high copy number of TLR7 
confers risk for BD in a Chinese Han population. (http://www.chictr.org number, 
ChiCTR-CCC-12002184.).