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Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene.

ABSTRACT: A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case-control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.

SUBMITTER: Lofgren SE

PROVIDER: S-EPMC3640319 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene.

Löfgren S E SE Frostegård J J Truedsson L L Pons-Estel B A BA D'Alfonso S S Witte T T Lauwerys B R BR Endreffy E E Kovács L L Vasconcelos C C Martins da Silva B B Kozyrev S V SV Alarcón-Riquelme M E ME

Genes and immunity 20120105 3

A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697 ...[more]

PMID: 22218224

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Project description:Background and objectivemiRNA-146a is a microRNA that plays an important role in systemic lupus erythematosus (SLE). Several studies have examined the role of miRNA-146a in SLE, but have demonstrated equivocal or even contradictory conclusions. Therefore, this meta-analysis aimed to assess the role of miRNA-146a in SLE by examining data from previous studies.MethodsA meta-analysis of relevant papers published before August 31, 2019, in the WanFang, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and Web of Science databases was performed to verify the relationship of miRNA-146a expression level to SLE. Two investigators independently extracted the data and conducted a quality assessment of the studies. All statistical analyses were performed using Stata 14.0. Trial sequence analysis (TSA) was conducted to assess the quality and strength of the studies using the TSA software.ResultsSix publications, involving 151 SEL patients and 132 healthy individuals as controls were included in this meta-analysis. The results showed that the expression of miRNA-146a was associated with SLE risk [standard mean difference (SMD) = -1.21, 95% confidence interval (95% CI) (-2.18, -0.23), P = .015]. The stratified analysis revealed that the expression of miRNA-146a was highly related to higher SLE risk among Asian (SMD = -1.30, 95% CI (-2.52, -0.07), P = .038) and Caucasian (SMD = -0.72, 95% CI (-1.20, -0.24), P = .003) populations. Besides, the serum levels of miRNA146a were significantly different (SMD = -1.73, 95% CI (-3.11, -0.36), P = .014). The TSA revealed that the cumulative Z-curve crossed the typical boundary value, and reached the TSA monitoring boundary, but did not reach the required information size. This indicates that even if the cumulative sample size did not meet required information size, no more trials were needed and a reliable conclusion was reached in advance. Sensitivity analyses indicated the instability of the meta-analysis.ConclusionsOverall, the expression of miRNA-146a is associated with SLE risk. Therefore, miRNA-146a is a promising candidate for the effective diagnosis of SLE. But, due to the limitations of this study, it is necessary to cautiously explain the results of this study.Systematic review registrationPROSPERO CRD42019151381.

Dataset Information

Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene.

Publications

Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene.

Similar Datasets

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