Dataset Information

Functional BDNF rs7124442 Variant Regulated by miR-922 is Associated with Better Short-Term Recovery of Ischemic Stroke.

ABSTRACT: Background:Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin, which contributes to the neuronal survival and synaptic plasticity. This study investigated the associations of BDNF polymorphisms at the 3'-untranslated region with risk and outcome of ischemic stroke in a Chinese Han population. Methods:500 patients and 520 controls were enrolled for BDNF rs7124442 genotyping. The binding of miR-922 to BDNF rs7124442 was examined by luciferase assay; BDNF expression was assessed using qRT-PCR. Results:Alcohol consumption, cigarette smoking, diabetes, hypertension (all P < 0.001) and higher serum triglycerides concentration (P = 0.009) were associated with an increased risk of developing ischemic stroke. After adjusted for age and sex, logistic regression analysis showed that IS patients harbored with rs7124442 TC genotype had a milder initial stroke (Dominant model: OR = 0.45, 95% CI = 0.25-0.81, P = 0.015), and also showed a better short-term recovery (Dominant model: OR = 0.39, 95% CI =0.24-0.68, P = 0.003). Furthermore, we found that co-transfection of hsa-miR-922 mimics with BDNF 3'-UTR containing the mutated allele C changed luciferase activity when compared to co-transfection with BDNF 3'-UTR containing the wild-type allele. Besides, patients carrying BDNF rs712444 TC or CC genotype had an increased level of BDNF compared with patients with the TT genotype. Conclusion:Our study demonstrates that the SNP rs7124442 in BDNF 3'-UTR, through affecting the regulatory role of miR-922 in BDNF expression, might act as a protective factor for the outcome of patients with ischemic stroke.

SUBMITTER: Liu B

PROVIDER: S-EPMC6875495 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Functional BDNF rs7124442 Variant Regulated by miR-922 is Associated with Better Short-Term Recovery of Ischemic Stroke.

Liu Binghui B He Wei W Liu Dinghua D

Therapeutics and clinical risk management 20191120

<h4>Background</h4>Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin, which contributes to the neuronal survival and synaptic plasticity. This study investigated the associations of <i>BDNF</i> polymorphisms at the 3'-untranslated region with risk and outcome of ischemic stroke in a Chinese Han population.<h4>Methods</h4>500 patients and 520 controls were enrolled for <i>BDNF</i> rs7124442 genotyping. The binding of miR-922 to <i>BDNF</i> rs7124442 was examined by lucife ...[more]

PMID: 31819463

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Project description:miRNAs are small non-coding RNAs modulating gene expression, and variants in miRNA genes are involved in the pathogenesis of ischemic stroke (IS). However, the effect of miR-34a polymorphisms on IS susceptibility has rarely been reported. In the present study, we investigated the association between rs12128240, rs2666433, and rs6577555 of the miR-34a gene and IS susceptibility. Snapshot assay was used to detect miR-34a polymorphisms in 548 IS patients and 560 controls. Relative expression of miR-34a was measured by quantitative real-time PCR. We found that rs2666433 was associated with a significantly increased risk of IS (AA vs. GG: OR = 1.61, 95% CI = 1.05-2.52, P = 0.031; AA vs. GG+GA: OR = 1.58, 95% CI = 1.05-2.45, P = 0.026). For the IS subtypes, rs2666433 was associated with large artery atherosclerosis (AA vs. GG: OR = 2.09, 95% CI = 1.16-3.51, P = 0.007; AA vs. GG+GA: OR = 2.02, 95% CI = 1.15-3.33, P = 0.007; A vs. G: OR = 1.36, 95% CI = 1.07-1.81, P = 0.021). Additionally, the level of miR-34a was significantly up-regulated in IS patients compared to the controls (P < 0.001), and patients with rs2666433 AA genotype had a higher level of miR-34a than those with GG+GA genotypes (P < 0.001). Furthermore, increased level of homocysteine was observed in IS patients compared to the controls (P < 0.001), especially in patients carrying the rs2666433AA genotype compared to those carrying the rs2666433 GG+GA genotypes (P < 0.001). However, no significant association between rs12128240 or rs6577555 and IS was found. Collectively, our study found the association between miR-34a polymorphisms and the risk of IS among the Chinese population. The results may provide an explanation for etiology of IS and a potential biomarker or therapeutic target for IS. HIGHLIGHTS-MiR-34a rs2666433 polymorphism was associated with an increased risk of ischemic stroke.-The level of miR-34a was significantly up-regulated in ischemic stroke patients compared with controls, and patients with rs2666433 AA genotype had a higher level miR-34a than those with GG+GA genotypes.-Furthermore, increased level of homocysteine was showed in IS patients compared to controls, and in patients carrying the rs2666433AA compared to those carrying the rs2666433 GG+GA.

Dataset Information

Functional BDNF rs7124442 Variant Regulated by miR-922 is Associated with Better Short-Term Recovery of Ischemic Stroke.

Publications

Functional BDNF rs7124442 Variant Regulated by miR-922 is Associated with Better Short-Term Recovery of Ischemic Stroke.

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