miRNA Copy Number Variants Confer Susceptibility to Acute Anterior Uveitis With or Without Ankylosing Spondylitis

Lu Yang, Liping Du, Yingying Yue, Yike Huang, Qingyun Zhou, Shuang Cao, Jian Qi, Liang Liang, Lili Wu, Chaokui Wang, Zi Ye, Yuan Tian, Aize Kijlstra, Shengping Hou*, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

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 x 10(-5) to 8.033 x 10(-9)). Additionally, the frequency of a low copy number of miR146a 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-1b 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(-).

Original languageEnglish
Pages (from-to)1991-2001
Number of pages11
JournalInvestigative Ophthalmology & Visual Science
Volume58
Issue number4
DOIs
Publication statusPublished - Apr 2017

Keywords

  • miRNA
  • CNVs
  • autoimmune disease
  • AAU(+)AS(+)
  • AAU(+)AS(-)
  • KOYANAGI-HARADA SYNDROME
  • NF-KAPPA-B
  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • PIGMENT EPITHELIAL-CELLS
  • OCULAR BEHCETS-DISEASE
  • DIAGNOSTIC-CRITERIA
  • MESSENGER-RNA
  • IMMUNE-SYSTEM
  • EXPRESSION
  • IL-6

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