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A functional polymorphism in the promoter of TUG1 is associated with an increased risk of ischaemic stroke.

ABSTRACT: Taurine-upregulated gene 1 (TUG1), a kind of long non-coding RNAs (lncRNAs), was up-regulated in ischaemic stroke (IS) with the function of promoting neuron apoptosis. In this study, we aimed to investigate the association of TUG1 polymorphisms with IS risk. The TUG1 polymorphisms were genotyped using a custom-by-design 48-Plex SNPscan kit. The promoter activity was measured using the dual luciferase reporter assay. Relative expression of TUG1 in IS patients was analysed using quantitative PCR and the binding of TUG1 rs2240183 polymorphism to transcription factor was analysed using chromatin immunoprecipitation (ChIP) assay. The rs2240183 CT/CC genotypes and C allele in the promoter of TUG1 were associated with an increased risk of IS (CT/CC vs. TT: adjusted OR = 1.70, 95% CI, 1.16-2.49, P = 0.006; C vs. T: adjusted OR = 1.47, 95% CI, 1.12-1.93, P = 0.005). Logistic regression analysis showed that the rs2240183 was a risk factor of IS besides TC, TG, HDL-C, LDL-C, VLDL-C, Apo-A1, Apo-B and NEFA. Further functional analysis revealed that the TUG1 rs2240183 C allele exhibited higher transcriptional activity and TUG1 expression levels (P < 0.01). The ChIP assay showed that the rs2240183 C allele binds to transcriptional factor GATA-1. These findings indicate that the rs2240183 C allele was associated with a higher risk of IS possibly by binding to GATA-1 and elevating TUG1 levels.

SUBMITTER: Wei YS

PROVIDER: S-EPMC6714496 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A functional polymorphism in the promoter of TUG1 is associated with an increased risk of ischaemic stroke.

Wei Ye-Sheng YS Yang Jun J He Yong-Ling YL Shi Xiang X Zeng Zhi-Neng ZN

Journal of cellular and molecular medicine 20190702 9

Taurine-upregulated gene 1 (TUG1), a kind of long non-coding RNAs (lncRNAs), was up-regulated in ischaemic stroke (IS) with the function of promoting neuron apoptosis. In this study, we aimed to investigate the association of TUG1 polymorphisms with IS risk. The TUG1 polymorphisms were genotyped using a custom-by-design 48-Plex SNPscan kit. The promoter activity was measured using the dual luciferase reporter assay. Relative expression of TUG1 in IS patients was analysed using quantitative PCR a ...[more]

PMID: 31264779

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Project description:BACKGROUND:The microRNA-17-92 (miR-17-92) cluster is one of the most extensively studied miRNA clusters. Abnormal expression of the cluster has been found to play important role in different kinds of human diseases, including ischemic stroke (IS). The aim of our study was to investigate the association between three polymorphisms (rs1491034, rs9301654 and rs982873) in the promoter of the miR-17-92 cluster and risk of IS. METHODS:Three hundred and ninety-eight patients with IS and 397 control subjects were included. The genotypes of the three polymorphisms were determined by Snapshot SNP genotyping assay. Relative expression of the cluster in peripheral blood mononuclear cells (PBMCs) of cases and controls were examined by quantitative real-time PCR. RESULTS:Significant association between rs9301654 polymorphism and risk of IS were observed basing on genotype, model and allele analyses (GA vs. AA: adjusted OR?=?0.63, 95% CI: 0.41~0.97, P?=?0.037; GG vs. AA: adjusted OR?=?0.23, 95% CI: 0.07~0.78, P?=?0.018; GA?+?GG vs. AA: adjusted OR?=?0.57, 95% CI: 0.38~0.87, P?=?0.009; GA?+?AA vs. GG: adjusted OR?=?0.27, 95% CI: 0.08~0.89, P?=?0.032; G vs. A: adjusted OR?=?0.58, 95% CI: 0.40~0.83). Haplotype analysis showed that TGC and TGT haplotypes were associated with decreased risk of IS (OR?=?0.59, 95% CI: 0.40~0.87, P?=?0.007 for TGC haplotype; OR?=?0.21, 95% CI: 0.06~0.75, P?=?0.009 for TGT haplotype). Importantly, we found the expression of miR-17-5p was significant higher while miR-19a-3p was significant lower in patient with IS compared with the control group (P?<?0.01), and patients with rs9301654GG or GA genotype displayed lower level of miR-19a-3p compared with the AA genotype (P?<?0.01). CONCLUSIONS:Our findings indicated that rs9301654 polymorphism in the promoter of miR-17-92 cluster may be associated with susceptibility of IS in the Chinese population. However, we found that rs9301654 polymorphism and its respective gene expression did not demonstrate consistent association with IS in the Chinese population. Further studies such as gene-gene interaction are warranted to reveal the role of miR-19a and its regulatory genes in the etiology of IS.

Dataset Information

A functional polymorphism in the promoter of TUG1 is associated with an increased risk of ischaemic stroke.

Publications

A functional polymorphism in the promoter of TUG1 is associated with an increased risk of ischaemic stroke.

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