Predisposition to Behcet's disease and VKH syndrome by genetic variants of miR-182

Hongsong Yu, Yunjia Liu, Lin Bai, Aize Kijlstra, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Web of Science)

Abstract

Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Beh double dagger et's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P = 3.36 Au 10(-4), OR = 0.55; P = 4.74 Au 10(-4), OR = 0.59) and VKH patients (P = 1.11 Au 10(-4), OR = 0.53; P = 1.26 Au 10(-4), OR = 0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P = 3.25 Au 10(-7), OR = 0.58; C allele: P = 1.81 Au 10(-7), OR = 0.60) and VKH (CC genotype: P = 7.89 Au 10(-8), OR = 0.57; C allele: P = 2.52 Au 10(-8), OR = 0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells (P = 2.1 Au 10(-2)). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH. MiR-182 contributes to genetic susceptibility of BD and VKH. No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed. Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed.
Original languageEnglish
Pages (from-to)961-967
JournalJournal of Molecular Medicine
Volume92
Issue number9
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Behcet's disease
  • Vogt-Koyanagi-Harada syndrome
  • miR-182
  • FoxO1
  • miR-27a
  • IL2RA

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