MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis

PLoS One. 2014 Mar 21;9(3):e91199. doi: 10.1371/journal.pone.0091199. eCollection 2014.

Abstract

Background: MicroRNA-146a (miR-146a) was a key negative regulator of autoimmunity. V-Ets oncogene homolog 1 (Ets-1) was demonstrated to bind to the miR-146a promoter region and markedly affects miR-146a promoter activity. This study aimed to investigate the association of miR-146a and Ets-1 gene polymorphisms with pediatric uveitis in a Han Chinese population.

Methodology/principal findings: A total of 520 patients and 1204 healthy controls were included in the present study. Five single-nucleotide polymorphisms (SNPs), miR-146a/rs2910164, miR-146a/rs57095329, miR-146a/rs6864584, ets-1/rs1128334 and ets-1/rs10893872 were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The expression of Ets-1 in peripheral blood mononuclear cells from genotyped healthy controls was tested by real-time PCR. Two SNPs (rs2910164 and rs10893872) were associated with pediatric uveitis in this study. The frequencies of the rs2910164 GG genotype and G allele were significantly increased (Pc = 3.11×10(-4); Pc = 2.75×10(-6)) while the CC genotype and C allele were significantly decreased (Pc = 0.001; Pc = 2.75×10(-6)) in patients compared with normal controls. The frequencies of the rs10893872 CC genotype and C allele were significantly increased (Pc = 3.89×10(-4); Pc = 0.01) while the CT genotype and T allele were significantly decreased (Pc = 0.004; Pc = 0.01) in patients compared with normal controls. The SNP rs2910164 GG genotype and G/C allele were also associated with the presence of microvascular leakage as detected by fundus fluorescein angiography in pediatric uveitis (Pc = 0.01; Pc = 0.005, respectively). Ets-1 expression in rs10893872 CC carriers was significantly higher than in CT and TT individuals (Pc = 0.013). There was no association of the other three SNPs with pediatric uveitis.

Conclusions: This study shows that miR-146a and Ets-1 are both associated with pediatric uveitis in Han Chinese. SNP rs10893872 may affect the genetic predisposition to pediatric uveitis by modulating expression of Ets-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Protein c-ets-1 / genetics*
  • Uveitis / genetics*

Substances

  • ETS1 protein, human
  • MIRN146 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Protein c-ets-1

Grants and funding

This work was supported by National Basic Research Program of China (973 Program)(2011CB510200), Key Project of Natural Science Foundation(81130019), Research Fund for the Doctoral Program of Higher Education of China (20115503110002), Clinic Key Project of Ministry of Health, Basic Research program of Chongqing, Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), Key Project of Health Bureau of Chongqing(2012-1-003) and Fund for PAR-EU Scholars Program. The authors have declared that no competing interests exist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.