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 x 10(-5); odds ratio [OR] = 2.0 and P-corr = 1.2 x 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 x 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 (Pcorr) = 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.