MicroRNA-146a and Ets-1 Gene Polymorphisms Are Associated with Pediatric Uveitis

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 (P(c) = 3.11×10(−4); P(c) = 2.75×10(−6)) while the CC genotype and C allele were significantly decreased (P(c) = 0.001; P(c) = 2.75×10(−6)) in patients compared with normal controls. The frequencies of the rs10893872 CC genotype and C allele were significantly increased (P(c) = 3.89×10(−4); P(c) = 0.01) while the CT genotype and T allele were significantly decreased (P(c) = 0.004; P(c) = 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 (P(c) = 0.01; P(c) = 0.005, respectively). Ets-1 expression in rs10893872 CC carriers was significantly higher than in CT and TT individuals (P(c) = 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.