Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

Buraczyńska, Monika; Żukowski, Paweł; Waciński, Piotr; Książek, Katarzyna; Załuska, Wojciech

doi:10.1016/j.jdiacomp.2014.05.006

Cited by 33 publications

(30 citation statements)

References 32 publications

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“…Firstly, we excluded 254 articles after title reviewing and duplicate screening. Then, 19 studies including 6 reviews, 12 studies not for focus polymorphisms, and 1 study without available information [22] were excluded. Finally, 12 eligible articles (13 studies) published from 2012 to 2016 were selected in the meta-analysis, including ten studies on microRNA-146a rs2910164 G>C [23–32], seven studies on microRNA-196a2 rs11614913 T>C [23, 26, 27, 29, 31, 33], six publications on microRNA-499 rs3746444 A>G [23, 25, 26, 29, 31, 33], and two studies on microRNA-149 rs71428439 A>G [29, 34], respectively.…”

Section: Resultsmentioning

confidence: 99%

Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility: a comprehensive meta-analysis involving 16484 subjects

et al. 2016

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Molecular epidemiological studies suggest that microRNA polymorphisms may be associated with an increased risk of coronary heart disease (CHD). However, the results of these studies were inconsistent and inconclusive. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between microRNA polymorphisms and CHD risk. PubMed, Embase, CNKI and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the association between microRNA-146a rs2910164, microRNA-196a2 rs11614913, microRNA-499 rs3746444 and microRNA-149 rs71428439 polymorphisms and CHD susceptibility. Heterogeneity, publication bias and sensitivity analysis were conducted to measure the robustness of our findings. A total of thirteen related studies involving 8,120 patients and 8,364 controls were analyzed. Significant associations between microRNA-146a rs2910164 polymorphism and CHD risk were observed in the total population, as well as in subgroup analysis. For microRNA-196a2 rs11614913 and microRNA-499 rs3746444, similarly increased risks were also found. In addition, no significant association was detected between microRNA-149 rs71428439 polymorphism and CHD risk. In conclusion, our meta-analyses suggest that microRNA polymorphisms may be associated with increased risk of CHD development.

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Section: Resultsmentioning

confidence: 99%

Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility: a comprehensive meta-analysis involving 16484 subjects

et al. 2016

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“…In light of studies showing that polymorphisms in human miRNA genes are strongly associated with disease susceptibility such as schizophrenia and diabetes323334, strategies such as ours are critical to improve our current understanding of the impact that genetic variants have on miRNA gene sequence affecting miRNA regulation and activity.…”

Section: Discussionmentioning

confidence: 99%

In vivo mutagenesis of miRNA gene families using a scalable multiplexed CRISPR/Cas9 nuclease system

Narayanan

Hill-Teran

Moro

et al. 2016

Sci Rep

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A large number of microRNAs (miRNAs) are grouped into families derived from the same phylogenetic ancestors. miRNAs within a family often share the same physiological functions despite differences in their primary sequences, secondary structures, or chromosomal locations. Consequently, the generation of animal models to analyze the activity of miRNA families is extremely challenging. Using zebrafish as a model system, we successfully provide experimental evidence that a large number of miRNAs can be simultaneously mutated to abrogate the activity of an entire miRNA family. We show that injection of the Cas9 nuclease and two, four, ten, and up to twenty-four multiplexed single guide RNAs (sgRNAs) can induce mutations in 90% of the miRNA genomic sequences analyzed. We performed a survey of these 45 mutations in 10 miRNA genes, analyzing the impact of our mutagenesis strategy on the processing of each miRNA both computationally and in vivo. Our results offer an effective approach to mutate and study the activity of miRNA families and pave the way for further analysis on the function of complex miRNA families in higher multicellular organisms.

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“…Emerging evidence suggests that miRs contribute to the pathogenesis of diabetes and diabetic complications (5,15,31,43). Since each miR has its potential targeting genes, information of miR involvement in diabetes is helpful for identification of the targeted molecules as well.…”

Section: Discussionmentioning

confidence: 99%

The SUR2B subunit of rat vascular K_ATP channel is targeted by miR-9a-3p induced by prolonged exposure to methylglyoxal

Jin

et al. 2015

American Journal of Physiology-Cell Physiology

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. The SUR2B subunit of rat vascular KATP channel is targeted by miR-9a-3p induced by prolonged exposure to methylglyoxal. Am J Physiol Cell Physiol 308: C139-C145, 2015. First published October 29, 2014; doi:10.1152/ajpcell.00311.2014.-ATP-sensitive K ϩ (KATP) channels regulate plasma membrane excitability. The Kir6.1/ SUR2B isoform of KATP channels is expressed in vascular smooth muscles and plays an important role in vascular tone regulation. This KATP channel is targeted by several reactive species. One of them is methylglyoxal (MGO), which is overly produced with persistent hyperglycemia and contributes to diabetic vascular complications. We have previously found that MGO causes posttranscriptional inhibition of the KATP channel, aggravating vascular tone regulation. Here we show evidence for the underlying molecular mechanisms. We screened microRNA databases and found several candidates. Of them, miR-9a-3p, increased its expression level by ϳ240% when the cultured smooth muscle cell line was exposed to micromolar concentrations of MGO. Treatments with exogenous miR-9a-3p downregulated the SUR2B but not Kir6.1 mRNA. Antisense nucleotides of miR9a-3p alleviated the effects of MGO. Quantitative PCR showed that the targeting sites of the miR-9a-3p were likely to be in the coding region of SUR2B. The effects of miR-9a-3p were mostly eliminated when the potential targeting site in SUR2B was site-specifically mutated. Our functional assays showed that KATP currents were impaired by miR-9a-3p induced with MGO treatment. These results suggest that MGO exposure raises the expression of miR-9a-3p, which subsequently downregulates the SUR2B mRNA, compromising KATP channel function in vascular smooth muscle.microRNA; ATP-sensitive potassium channel; diabetes DIABETES MELLITUS is a major challenge to biomedical sciences (12). Diabetes causes metabolic alterations leading to excessive production of various intermediary metabolites (4). One of them is methylglyoxal (MGO), a highly reactive carbonyl species (RCS) (2,16,39). MGO can react with proteins, nucleotides, and lipids, damaging these molecules and promoting inflammation and cell injuries (10,17,26). Normally, MGO is rapidly detoxified by metabolic and redox enzymes so that it is maintained at a rather low level (37). Under diabetic conditions, however, the increased production of precursor molecules and impaired carbonyl detoxification system result in overproduction and accumulation of this RCS (38). The imbalance in the production and clearance of RCS then leads to carbonyl stress, which is known to play an important role in the development of diabetic complications, especially in the vasculature (1, 7, 11).In the vasculature, an increase in MGO levels can impair structure and function of the vascular walls by acting on the vascular smooth muscle (VSM), endothelium, or both. This in turn disrupts the signaling network in these cells, triggers structural remodeling of the vascular wall, propagates vascular inflammation, and causes vascular dysfunction (40 -42). Ind...

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Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

Cited by 33 publications

References 32 publications

Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility: a comprehensive meta-analysis involving 16484 subjects

Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility: a comprehensive meta-analysis involving 16484 subjects

In vivo mutagenesis of miRNA gene families using a scalable multiplexed CRISPR/Cas9 nuclease system

The SUR2B subunit of rat vascular K_ATP channel is targeted by miR-9a-3p induced by prolonged exposure to methylglyoxal

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