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

<h4>Background</h4>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...

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Autores principales: Lin Wei, Qingyun Zhou, Shengping Hou, Lin Bai, Yunjia Liu, Jian Qi, Qin Xiang, Yan Zhou, Aize Kijlstra, Peizeng Yang
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spelling oai:doaj.org-article:ff76c947853444d79bfc29b76da7fcca2021-11-18T08:26:52ZMicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.1932-620310.1371/journal.pone.0091199https://doaj.org/article/ff76c947853444d79bfc29b76da7fcca2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24658012/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Lin WeiQingyun ZhouShengping HouLin BaiYunjia LiuJian QiQin XiangYan ZhouAize KijlstraPeizeng YangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91199 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lin Wei
Qingyun Zhou
Shengping Hou
Lin Bai
Yunjia Liu
Jian Qi
Qin Xiang
Yan Zhou
Aize Kijlstra
Peizeng Yang
MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format article
author Lin Wei
Qingyun Zhou
Shengping Hou
Lin Bai
Yunjia Liu
Jian Qi
Qin Xiang
Yan Zhou
Aize Kijlstra
Peizeng Yang
author_facet Lin Wei
Qingyun Zhou
Shengping Hou
Lin Bai
Yunjia Liu
Jian Qi
Qin Xiang
Yan Zhou
Aize Kijlstra
Peizeng Yang
author_sort Lin Wei
title MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.
title_short MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.
title_full MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.
title_fullStr MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.
title_full_unstemmed MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis.
title_sort microrna-146a and ets-1 gene polymorphisms are associated with pediatric uveitis.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/ff76c947853444d79bfc29b76da7fcca
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