Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

Huang, Suli; Zhou, Shuling; Zhang, Yanwei; Lv, Ziquan; Li, Shanshan; Xie, Chan; Ke, Yuebin; Deng, Pingjian; Yang, Geng; Zhang, Qian; Chu, Xun; Yi, Zhaohui; Zhang, Ying; Wu, Tangchun; Cheng, Jinquan

doi:10.1371/journal.pone.0117007

Cited by 45 publications

(54 citation statements)

References 33 publications

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“…The homozygous GG genotype exerted no noticeable effect on the susceptibility in this study, which might be due to the limited sample size of subjects with GG genotype (only 18.3% or 19.8% in the populations). The miR-146a C>G polymorphism has also been reported to associate with the risk of ischemic stroke (Jeon et al 2013;Huang et al 2015), which indicates that ACS or CHD may share genetic risk factors with ischemic stroke. Although rs11614913 was associated with an increased risk of ACS in the females, we found no association in the whole population.…”

Section: Discussionmentioning

confidence: 99%

“…miRNAs are initially transcribed as primary miRNA (pri-miRNA) and then processed into hairpin-structured precursor miRNAs (pre-miRNAs), which are the direct precursor of mature miRNAs with approximately 70 nucleotides in length (Lee et al 2003). Two well-studied miRNA polymorphisms located in the pre-miRNA sequences (miR-146a rs2910164 C>G and miR-196a2 rs11614913 T>C) have been found to be associated with various diseases (Xu et al 2009;Xiong et al 2014;Huang et al 2015). Moreover, the rs2910164 C>G was found to be able to reduce the expression of mature miR-146a and thus affect the binding with target mRNA (Jazdzewski et al 2008;Xu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population

Huang

Deng

et al. 2015

Tohoku J. Exp. Med.

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MicroRNAs (miRNAs) can contribute to the development of cardiovascular diseases, and single nucleotide polymorphisms (SNPs) in miRNA genes may influence disease susceptibility by altering mature miRNA expression levels. However, the effect of SNPs located in miR-146a and miR-196a2 genes on risk of acute coronary syndrome (ACS) has not been reported in the Chinese population. Two miRNA polymorphisms located in miRNA genes (miR-146a rs2910164 C>G and miR-196a2 rs11614913 T>C) were genotyped in 722 ACS patients and 721 control subjects. The CG genotype of rs2910164 was significantly associated with decreased risk of ACS [CG vs. CC, odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.55-0.95, P = 0.020; dominant model, OR = 0.77, 95% CI: 0.60-0.99, P = 0.044]. We did not find any association of rs11614913 with the risk of ACS. Stratification analysis showed that the rs2910164 CG genotype was associated with decreased risk of ACS (dominant model) in males, subjects with body mass index more than 24 kg/m 2 , and in hypertensive subjects. Significant combined effects were also observed between rs2910164 and blood lipids or C-reactive protein levels. In summary, this study provides the first evidence that the CG genotype of miR-146a rs2910164 is associated with a significantly decreased risk of ACS in a Chinese population. Moreover, rs2910164 and blood lipids or an inflammatory marker may have a combined effect on the onset of ACS. These findings indicate that miR-146a rs2910164 may act as a novel molecular marker for ACS susceptibility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population

Huang

Deng

et al. 2015

Tohoku J. Exp. Med.

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“…The miRNA‐499 gene is located on 20q11.22, and the SNP rs3746444 lies in the 3p strand of the mature miRNA‐499 sequences. A nucleotide mutation from A to G in miRNA‐499 has been found in many diseases , such as biliary atresia (BA) , tumors , ossification of the posterior longitudinal ligament (OPLL) , coronary artery disease (CAD) and ischaemic stroke .…”

Section: Mirna‐137mentioning

confidence: 99%

Associations ofmicroRNAsingle nucleotide polymorphisms and disease risk and pathophysiology

2017

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Single nucleotide polymorphisms (SNPs) are genetic variations that contribute to human phenotypes associated with various diseases. SNPs are involved in the regulation of a broad range of physiological and pathological processes, such as cellular senescence, apoptosis, inflammation, and immune response, by upregulating the expression of classical inflammation markers. Recent studies have suggested that SNPs located in gene-encoding microRNAs (miRNAs) affect various aspects of diseases by regulating the expression or activity of miRNAs. In the last few years, miRNA polymorphisms that increase and/or reduce the risk of developing many diseases, such as cancers, autoimmune diseases, and cardiovascular diseases, have attracted increasing attention not only because of their involvement in the pathophysiology of diseases but also because they can be used as prognostic biomarkers for a variety of diseases. In this review, we summarize the relationships between miRNA SNPs and the pathophysiology and risk of diseases.

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“…Genetic variability at miR-146a loci seems to be unrelated to T2DM incidence; inconclusive data were reported on the association between single nucleotide polymorphism (SNP) rs2910164 of miR-146a gene and T2DM incidence in a large cohort of Chinese Han subjects [80, 81]. However, miR-146a/rs2910164 and fasting glucose have been reported to exert significant combined effects on ischemic stroke susceptibility [81].…”

Section: Introductionmentioning

confidence: 99%

“…However, miR-146a/rs2910164 and fasting glucose have been reported to exert significant combined effects on ischemic stroke susceptibility [81]. …”

Section: Introductionmentioning

confidence: 99%

Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes

et al. 2015

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The development of type-2 diabetes mellitus (T2DM) and its complications is largely due to the complex interaction between genetic factors and environmental influences, mainly dietary habits and lifestyle, which can either accelerate or slow down disease progression. Recent findings suggest the potential involvement of epigenetic mechanisms as a crucial interface between the effects of genetic predisposition and environmental factors. The common denominator of environmental factors promoting T2DM development and progression is that they trigger an inflammatory response, promoting inflammation-mediated insulin resistance and endothelial dysfunction. Proinflammatory stimuli, including hyperglycemia, oxidative stress, and other inflammatory mediators, can affect epigenetic mechanisms, altering the expression of specific genes in target cells without changes in underlying DNA sequences. DNA methylation and post-translational histone modifications (PTHMs) are the most extensively investigated epigenetic mechanisms. Over the past few years, non-coding RNA, including microRNAs (miRNAs), have also emerged as key players in gene expression modulation. MiRNAs can be actively released or shed by cells in the bloodstream and taken up in active form by receiving cells, acting as efficient systemic communication tools. The miRNAs involved in modulation of inflammatory pathways (inflammamiRs), such as miR-146a, and those highly expressed in endothelial lineages and hematopoietic progenitor cells (angiomiRs), such as miR-126, are the most extensively studied circulating miRNAs in T2DM. However, data on circulating miRNA signatures associated with specific diabetic complications are still lacking. Since immune cells and endothelial cells are primarily involved in the vascular complications of T2DM, their relative contribution to circulating miRNA signatures needs to be elucidated. An integrated approach encompassing different epigenetic mechanisms would have the potential to provide new mechanistic insights into the genesis of diabetes and its severe vascular complications and identify a panel of epigenetic markers with diagnostic/prognostic and therapeutic relevance.

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Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

Cited by 45 publications

References 33 publications

A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population

A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population

Associations ofmicroRNAsingle nucleotide polymorphisms and disease risk and pathophysiology

Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes

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