Association Between Copy Number Variations of TLR7 and Ocular Behçet's Disease in a Chinese Han Population

Invest Ophthalmol Vis Sci. 2015 Feb 3;56(3):1517-23. doi: 10.1167/iovs.14-15030.


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. ( number, ChiCTR-CCC-12002184.).

Keywords: Behçet's disease; Toll-like receptor; Toll-like receptor 7; Vogt-Koyanagi-Harada syndrome; acute anterior uveitis; ankylosing spondylitis; copy number variants; uveitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Behcet Syndrome / ethnology*
  • Behcet Syndrome / genetics*
  • Case-Control Studies
  • China
  • Chromosomes, Human, X / genetics
  • Cytokines / metabolism
  • DNA Copy Number Variations / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Prospective Studies
  • RNA, Messenger / genetics
  • Spondylitis, Ankylosing / ethnology
  • Spondylitis, Ankylosing / genetics
  • Toll-Like Receptor 7 / genetics*
  • Uveitis / ethnology*
  • Uveitis / genetics*
  • Uveitis, Anterior / ethnology
  • Uveitis, Anterior / genetics
  • Uveomeningoencephalitic Syndrome / ethnology
  • Uveomeningoencephalitic Syndrome / genetics


  • Cytokines
  • RNA, Messenger
  • TLR7 protein, human
  • Toll-Like Receptor 7

Associated data

  • ChiCTR/CHICTR-CCC-12002184