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      Association of polymorphisms in MALAT1 with risk of coronary atherosclerotic heart disease in a Chinese population

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          Abstract

          Background

          Metastasis associated lung adenocarcinoma transcript 1 ( MALAT1) plays an important role in vascular remodeling. Down-regulation of MALAT1 can inhibit the proliferation of vascular endothelial cells and vascular smooth muscle cells, reduce cardiomyocyte apoptosis and improve left ventricular function, which is closely linked to numerous pathological processes such as coronary atherosclerotic heart disease (CAD). The aim of this study was to investigate whether polymorphisms in MALAT1 were associated with the susceptibility to CAD.

          Methods

          A total of 508 CAD patients and 562 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in MALAT1 (i.e., rs11227209, rs619586, rs664589, and rs3200401) were genotyped using a TaqMan allelic discrimination assay.

          Results

          The rs619586 AG/GG genotypes and G allele were associated with a reduced risk of CAD (AG/GG vs. AA: adjusted OR = 0.66, 95% CI: 0.48–0.91; G vs. A: adjusted OR = 0.68, 95% CI: 0.51–0.90). Stratification analyses showed that CAD patients with rs11227209 CG/GG, rs619586 AG/GG, and rs3200401 CT/TT genotypes exhibited lower levels of TCH ( P = 0.02, 0.04, and 0.02, respectively). Moreover, CGCC haplotype was associated with a decreased risk of CAD (OR = 0.28, 95% CI: 0.16–0.48). Multivariate logistic regression analysis identified some independent risk factors for CAD, including rs619586 and rs664589. Subsequent combined analysis showed that the combined genotypes of rs619586AG/GG and rs664589CC were associated with a reduced risk of CAD (OR = 0.29; 95%CI, 0.16–0.53).

          Conclusions

          These findings indicate that rs619586AG/GG genotypes in MALAT1 may protect against the occurrence of CAD.

          Electronic supplementary material

          The online version of this article (10.1186/s12944-018-0728-2) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          TGF-β-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12.

          TGF-β promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). However, the underlying mechanisms causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown to play important regulatory roles in cancer progression. The lncRNA malat1 (metastasis associated lung adenocarcinoma transcript 1) is a critical regulator of the metastasis phenotype of lung cancer cells. We, therefore, investigated whether TGF-β regulates malat1 expression to promote tumor metastasis of bladder cancer. The expression levels of malat1 and EMT markers were assayed in specimens of bladder cancer. The role of malat1 in regulating bladder cancer metastasis was evaluated in cell and animal models. TGF-β induces malat1 expression and EMT in bladder cancer cells. malat1 overexpression is significantly correlated with poor survival in patients with bladder cancer. malat1 and E-cadherin expression is negatively correlated in vitro and in vivo. malat1 knockdown inhibits TGF-β-induced EMT. malat1 is associated with suppressor of zeste 12 (suz12), and this association results in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression. Furthermore, targeted inhibition of malat1 or suz12 suppresses the migratory and invasive properties induced by TGF-β. Finally, we demonstrated that malat1 or suz12 knockdown inhibits tumor metastasis in animal models. These data suggest that malat1 is an important mediator of TGF-β-induced EMT, and suggest that malat1 inhibition may represent a promising therapeutic option for suppressing bladder cancer progression. ©2014 AACR.
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            Genetics of coronary artery disease: discovery, biology and clinical translation

            The past decade has seen tremendous progress in understanding the genetic architecture of coronary artery disease (CAD). Khera and Kathiresan review research efforts that have improved our understanding of the genetic drivers of CAD, and discuss the promises and challenges of integrating genetic information into routine clinical practice.
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              Genetics of Coronary Artery Disease.

              Genetic factors contribute importantly to the risk of coronary artery disease (CAD), and in the past decade, there has been major progress in this area. The tools applied include genome-wide association studies encompassing >200,000 individuals complemented by bioinformatic approaches, including 1000 Genomes imputation, expression quantitative trait locus analyses, and interrogation of Encyclopedia of DNA Elements, Roadmap, and other data sets. close to 60 common SNPs (minor allele frequency>0.05) associated with CAD risk and reaching genome-wide significance (P<5 × 10(-8)) have been identified. Furthermore, a total of 202 independent signals in 109 loci have achieved a false discovery rate (q<0.05) and together explain 28% of the estimated heritability of CAD. These data have been used successfully to create genetic risk scores that can improve risk prediction beyond conventional risk factors and identify those individuals who will benefit most from statin therapy. Such information also has important applications in clinical medicine and drug discovery by using a Mendelian randomization approach to interrogate the causal nature of many factors found to associate with CAD risk in epidemiological studies. In contrast to genome-wide association studies, whole-exome sequencing has provided valuable information directly relevant to genes with known roles in plasma lipoprotein metabolism but has, thus far, failed to identify other rare coding variants linked to CAD. Overall, recent studies have led to a broader understanding of the genetic architecture of CAD and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on CAD risk. Despite this success, there has been limited progress in understanding the function of the novel loci; the majority of which are in noncoding regions of the genome.
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                Author and article information

                Contributors
                86-871-63211330 , 895912415@qq.com
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                10 April 2018
                10 April 2018
                2018
                : 17
                : 75
                Affiliations
                GRID grid.452826.f, Department of Heart Vascular Surgery, , Yan’An Hospital Affiliated to Kunming Medical University, ; Kunming, 650051 Yunnan People’s Republic of China
                Article
                728
                10.1186/s12944-018-0728-2
                5891990
                29631611
                9729e9a2-d63c-4220-bec1-558831ee75b3
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 February 2018
                : 28 March 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Biochemistry
                metastasis associated lung adenocarcinoma transcript 1,polymorphism,coronary atherosclerotic heart disease

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