Purpose: To investigate the association of microRNA (miRNA) copy number variants (CNVs) with acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS) and to assess underlying disease mechanisms.
Methods: This study included 768 patients with AAU+AS+ or AAU+AS- and 660 controls from a Chinese Han population. Genotyping of CNVs was performed by TaqMan PCR. The expression of miRNAs, transfection efficiency of miR-9-3, and cytokine production were measured by real-time PCR, flow cytometry, or ELISA.
Results: The frequency of low copy numbers of miR-143, miR-146a, miR-9-3, and miR-205 and of high copy numbers of miR-301a and miR-23a was increased in patients with AAU+AS+ (P = 3.725 × 10-5 to 8.033 × 10-9). Additionally, the frequency of a low copy number of miR-146a and a high copy number of miR-23a and miR-205 was significantly increased in AAU+AS- patients (P = 0.002-0.001). The frequency of low copy number of miR-205 was increased in AAU+AS+ compared with AAU+AS- (P = 0.001). The mRNA expression of miR-9-3 was significantly decreased in patients with AAU+AS+ compared with controls and positively associated with its copy number. Additionally, the production of IL-1β and IL-6 was shown to be regulated by miR-9-3 in human primary retinal pigment epithelial cells.
Conclusions: Low gene copy numbers of miR-143, miR-146a, miR-9-3, miR-205 and high gene copy numbers of miR-301a and miR-23a were associated with susceptibility to AAU+AS+. A low copy number of miR-146a and a high copy number of miR-23a and miR-205 were associated with AAU+AS-.