A 3′ Untranslated Region Polymorphism of CTNNB1 (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

2021 ◽  
pp. 1-11
Author(s):  
Xin-Yi Zhao ◽  
Shu-Yan Hu ◽  
Jia-Lei Yang ◽  
Xing-Mei Chen ◽  
Xian-Li Huang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Mrna Expression ◽  
Binding Site ◽  
Untranslated Region ◽  
Luciferase Activity ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Artery Disease

<b><i>Background:</i></b> <i>CTNNB1</i> is reported to be related to the pathological process of ischemic stroke (IS) and coronary artery disease (CAD). Polymorphism located in the 3′ untranslated region (3′UTR) of a gene might affect gene expression by modifying binding sites for microRNAs (miRNAs). This study aimed to analyze the association between polymorphism rs2953, which locates in the 3′UTR of <i>CTNNB1,</i> and the risk of IS and CAD. <b><i>Methods:</i></b> The <i>CTNNB1</i> messenger RNA (mRNA) expression level in peripheral venous blood was measured. In total, 533 patients with IS, 500 patients with CAD, and 531 healthy individuals were genotyped by Sequenom Mass­Array technology. The binding of miR-3161 to <i>CTNNB1</i> was determined by dual-luciferase reporter assay. <b><i>Results:</i></b> The <i>CTNNB1</i> mRNA expression level for the IS group was significantly lower than that for the control group. Rs2953 was significantly associated with both IS risk and CAD risk. Significant association was also found between polymorphism rs2953 and many conventional factors, such as serum lipid level, blood coagulation markers, blood glucose level, and homocysteine level in patients. Rs2953 T allele introduced a binding site to miRNA-3161 and thus decreased luciferase activity. <b><i>Conclusion:</i></b> Polymorphism rs2953 is associated with the risk of both IS and CAD. Moreover, polymorphism rs2953 (T) introduces a binding site to miRNA-3161 and thus decreases luciferase activity in cell lines.

scholarly journals Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Martin Bahls ◽  
Michael F. Leitzmann ◽  
André Karch ◽  
Alexander Teumer ◽  
Marcus Dörr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Artery Disease

Abstract Aims Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. Methods and results We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. Conclusions These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. Graphic abstract

scholarly journals Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics

2018 ◽  
Vol 115 (48) ◽  
pp. E11349-E11358 ◽  
Author(s):  
Matthew D. Krause ◽  
Ru-Ting Huang ◽  
David Wu ◽  
Tzu-Pin Shentu ◽  
Devin L. Harrison ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Enhancer Activity ◽  
Protective Allele ◽  
Unidirectional Flow ◽  
Artery Disease

Biomechanical cues dynamically control major cellular processes, but whether genetic variants actively participate in mechanosensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation of vascular endothelium contributing to atherosclerosis, the major cause of coronary artery disease (CAD) and ischemic stroke (IS). Conversely, unidirectional flow promotes quiescent endothelium. Genome-wide association studies (GWAS) have identified chromosome 1p32.2 as strongly associated with CAD/IS; however, the causal mechanism related to this locus remains unknown. Using statistical analyses, assay of transposase accessible chromatin with whole-genome sequencing (ATAC-seq), H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs), our results demonstrate that rs17114036, a common noncoding polymorphism at 1p32.2, is located in an endothelial enhancer dynamically regulated by hemodynamics. CRISPR-Cas9–based genome editing shows that rs17114036-containing region promotes endothelial quiescence under unidirectional shear stress by regulating phospholipid phosphatase 3 (PLPP3). Chromatin accessibility quantitative trait locus (caQTL) mapping using HAECs from 56 donors, allelic imbalance assay from 7 donors, and luciferase assays demonstrate that CAD/IS-protective allele at rs17114036 in PLPP3 intron 5 confers increased endothelial enhancer activity. ChIP-PCR and luciferase assays show that CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. These results demonstrate that a human SNP contributes to critical endothelial mechanotransduction mechanisms and suggest that human haplotypes and related cis-regulatory elements provide a previously unappreciated layer of regulatory control in cellular mechanosensing mechanisms.

scholarly journals GW26-e2222 Polymorphisms in the DOCK7 gene and the risks of coronary artery disease and ischemic stroke

2015 ◽  
Vol 66 (16) ◽  
pp. C268 ◽  
Author(s):  
Rongjun Nie ◽  
Tao Guo ◽  
Xiaoli Cao ◽  
Wuxian Chen ◽  
Jinzhen Wu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Artery Disease

Association of ischemic stroke to coronary artery disease using computed tomography coronary angiography

2012 ◽  
Vol 160 (3) ◽  
pp. 171-174 ◽  
Author(s):  
Jesper K. Jensen ◽  
Hector M. Medina ◽  
Bjarne L. Nørgaard ◽  
Kristian A. Øvrehus ◽  
Jesper M. Jensen ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Computed Tomography Coronary Angiography ◽  
Artery Disease
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