Dataset Information

Lack of association of miR-146a and Ets-1 gene polymorphisms with Fuchs uveitis syndrome in Chinese Han patients.

ABSTRACT: PURPOSE: The aim of this study was to investigate the potential association of microRNA-146a (miR-146a) and V-Ets oncogene homolog 1 (Ets-1) gene polymorphisms with Fuchs Uveitis syndrome (FUS). METHODS: Three single-nucleotide polymorphisms (SNPs), miR-146a/rs2910164, ets-1/rs1128334, and ets-1/rs10893872 were genotyped in 219 Han Chinese patients with FUS and 612 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype counts were analyzed by the ?² test. RESULTS: No significant difference concerning the genotypic and allelic frequencies of rs2910164, rs1128334, and rs10893872 polymorphisms could be found between patients with FUS and the normal controls. Analysis according to gender did not show any influence of sex on the association of miR-146a and Ets-1 with FUS. CONCLUSIONS: Our results suggest that the investigated three SNPs, miR-146a/rs2910164, ets-1/rs1128334, and ets-1/rs10893872, are not associated with FUS in the Han Chinese population.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC3283209 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Lack of association of miR-146a and Ets-1 gene polymorphisms with Fuchs uveitis syndrome in Chinese Han patients.

Zhou Qingyun Q Kijlstra Aize A Hou Shengping S Yu Hongsong H Zhang Xuedong X Li Xinyu X Xiao Xiang X Yang Peizeng P

Molecular vision 20120211

<h4>Purpose</h4>The aim of this study was to investigate the potential association of microRNA-146a (miR-146a) and V-Ets oncogene homolog 1 (Ets-1) gene polymorphisms with Fuchs Uveitis syndrome (FUS).<h4>Methods</h4>Three single-nucleotide polymorphisms (SNPs), miR-146a/rs2910164, ets-1/rs1128334, and ets-1/rs10893872 were genotyped in 219 Han Chinese patients with FUS and 612 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genoty ...[more]

PMID: 22355253

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Project description:BackgroundMicroRNA-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 findingsA 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.ConclusionsThis 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.

Project description:BackgroundPolymorphisms of microRNA (miRNA), as a novel mechanism, are closely associated with disease states by interfering with miRNA function. Direct correlations have been identified between single-nucleotide polymorphisms (SNPs) in miRNA, but the effect on type 2 diabetes mellitus (T2DM) onset among Chinese population remains unclear. Therefore, the aim of this study was to identify correlations between common SNPs in miR-27a, miR-146a, and miR-124a with T2DM among a Chinese population, as well as to explore diabetic pathological mechanisms and the impact of environmental factors.MethodsSNPscan technology was used to genotype 995 patients newly diagnosed with T2DM and 967 controls. Logistic regression analysis was performed to compare mutation frequencies between cases and controls.ResultsWe found no significant correlations between all genotypes of these miRNAs and T2DM in our research. However, stratification analysis identified a lower risk of T2DM associated with the rs531564GC genotype among younger subjects (age < 45 years) (adjusted P = 0.043; odds ratio [OR] = 0.73; 95% confidence interval [CI] = 0.54-0.99). Furthermore, the rs895819CC genotype in overweight people (24 ≤ body mass index [BMI] < 28) was significantly associated with an increased risk of T2DM (adjusted P = 0.042; OR = 1.73; 95% CI = 1.02-2.94), while the rs2910164 genotype in miR-146a was not significantly correlated with T2DM. The genetic risk score was calculated based on the number of risk alleles of the three SNPs and was found to be correlated to total cholesterol (adjusted P = 0.021).ConclusionsThe rs531564GC genotype acted as a protective factor to decrease the risk of T2DM in younger subjects (age < 45 years), while the presence of the rs895819CC genotype increased the risk of illness among overweight subjects (24 ≤ BMI < 28 kg/m 2 ). The presence of SNPs in miRNA might promote disease by affecting miRNA expression and gene function. Thus, miRNA mimics or inhibitors that directly regulate miRNA expression present novel and promising therapeutic targets.

Project description:Posner-Schlossman-Syndrome (PSS) is clinically characterized by acute, recurrent, mild, unilateral uveitis anterior accompanied by elevated intraocular pressure (IOP). Fuchs´ Uveitis (FU) is a chronic, low-grade-inflammatory disorder, involving anterior uvea and vitreous. The clinical findings show remarkable similarities as well as differences. In our study, we determine the composition of immune mediators in aqueous humor of patients with PSS and FU and evaluate if immune mediators play a crucial role in specific viral intraocular inflammation and IOP rises. Aqueous humor samples from 81 uveitis patients (= eyes) presenting with either PSS or FU were collected at one time point. Local intraocular antibody synthesis to rubella virus was confirmed in 65 patients, whereas 16 were tested positively for human cytomegalovirus. Thirteen patients with PSS and 10 patients with FU were treated with glaucoma medications. Additionally, 11 cataract patients acted as control group. Immune mediator concentrations were measured by Bio-Plex Pro assay. We observed in both PSS (IFN-γ: 174.9 pg/mL; TNF-α: 25.1 pg/mL) and FU (IFN-γ: 25.4 pg/mL; TNF-α: 27.2 pg/mL) groups a significantly increased level of T-helper 1 immune mediators compared to controls (IFN-γ, TNF-α: 0 pg/mL) [median]. Notably, PSS patients (IL-1RA: 73.4 pg/mL; IL-8: 199.4 pg/mL; IL-10: 33.4 pg/mL; IP-10: 126350 pg/mL) showed a stronger and more active ocular inflammatory response, than FU patients (IL-1RA: 4.3 pg/mL; IL-8: 72.4 pg/mL; IL-10: 1.6 pg/mL; IP-10: 57400 pg/mL). Furthermore, a negative correlation between mediators and IOP was seen in the PSS group, potentially caused by acetazolamide-treatment. Our findings show that immune mediators play a crucial role in specific viral intraocular inflammation and influence IOP levels. Remarkable similarities but also significant differences of immune mediator concentrations are apparent in PSS compared to FU. High concentrations of IL-1RA, IL-8, IL-10, and IP-10 correlate with active inflammation in PSS, while FU may trigger chronic inflammation. Our data also substantiated a very similar composition of cytokines in those patients from the PSS group suffering from ocular hypertension and thus offers a potential explanation model for a negative correlation between mediators and IOP.

Dataset Information

Lack of association of miR-146a and Ets-1 gene polymorphisms with Fuchs uveitis syndrome in Chinese Han patients.

Publications

Lack of association of miR-146a and Ets-1 gene polymorphisms with Fuchs uveitis syndrome in Chinese Han patients.

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