Association of T-Bet, GATA-3, RORC, and FOXP3 Copy Number Variations With Acute Anterior Uveitis With or Without Ankylosing Spondylitis in Chinese Han.

PURPOSE: Acute anterior uveitis (AAU) is the most common form of uveitis and is a frequent ocular manifestation of ankylosing spondylitis (AS). Thymocyte CD4+ cells have been reported to play an important role in the pathogenesis of both AAU and AS. To test whether the copy number variations (CNVs) of CD4+ T cell transcription factor genes including T-bet, GATA binding protein 3 (GATA)-3, related orphan receptor C (RORC) and forkhead box protein 3 (FOXP3) are associated with acute anterior uveitis either in the presence or absence of ankylosing spondylitis (AAU+AS+; AAU+AS-).

METHODS

The study included 676 patients with AAU, including 298 patients with AAU+AS+, 378 patients with AAU+AS-, and 596 unrelated healthy controls in a Chinese Han population. Copy number variations were examined by real-time PCR.

RESULTS

The frequency of a high copy number (CN) of T-bet was increased in AAU+AS+ as well as AAU+AS- patients when compared with controls (P value after Bonferroni correction [P(corr)] = 4.3 × 10(-5); odds ratio [OR] = 2.0 and P(corr) = 1.2 × 10(-8); OR = 2.3, respectively). The frequency of a high CN of GATA-3 was significantly higher in AAU+AS+ patients than in controls (P(corr) = 1.8 × 10(-7); OR = 4.9). A higher frequency of CN of FOXP3 was found in female AAU+AS+ patients and female AAU+AS- patients (P(corr) = 0.005, OR = 5.9 and P(corr) = 0.004, OR = 4.9, respectively ). No association was found between CNVs of RORC and AAU+AS- or AAU+AS+ patients.

CONCLUSIONS

A high copy number of T-bet and GATA-3 confers susceptibility to AAU and AS, and a high copy number of FOXP3 confers susceptibility to female patients with AAU either with or without AS.