scholarly journals Identification of TFEB gene genetic variants in acute myocardial infarction

2020 ◽  
Author(s):  
Jie Zhang ◽  
Yexin Zhang ◽  
Xiaohui He ◽  
Shuai Wang ◽  
Shuchao Pang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Lipid Metabolism ◽  
Genetic Variants ◽  
Cultured Cells ◽  
Nucleotide Polymorphisms ◽  
Lysosomal Hydrolases ◽  
Mobility Shift ◽  
Altered Level ◽  
Lysosomal System

Abstract Background: Abnormal lipid metabolism and inflammation play critical roles in the initiation and progression of atherosclerosis and its associated complications, including coronary artery disease (CAD) and acute myocardial infarction (AMI). Autophagic-lysosomal system is involved in many physiological processes, such as lipid metabolism and inflammation. TFEB, a master regulator of the system, coordinates the expression of lysosomal hydrolases, lysosomal membrane proteins, and autophagic proteins. Altered level of TFEB gene expression and subsequent changes of autophagic-lysosomal system may be involved in the onset of CAD and AMI.Methods: In this study, the promoter of the TFEB gene was genetically and functionally analyzed in AMI patients (n=352) and ethnic-matched healthy controls (n=337).Results: A total of fifteen genetic variants, including eight single nucleotide polymorphisms (SNPs), were identified in the participants. Two novel genetic variants and four SNPs were only identified in six AMI patients, and significantly altered the transcriptional activity of the TFEB gene in cultured cells. Further electrophoretic mobility shift assay revealed that two genetic variants (g.41737144A>G and g.41736544C>T) and two SNPs [g.41737274T>C (rs533895008) and g.41736987C>T (rs760293138)] evidently affected the binding of transcription factors.Conclusions: Our findings suggested that the genetic variants in TFEB gene promoter may change TFEB levels, contributing to AMI as a low-frequency risk factor.

scholarly journals TFEB Gene Promoter Variants Effect on Gene Expression in Acute Myocardial Infarction

2021 ◽  
Vol 9 ◽  
Author(s):  
Jie Zhang ◽  
Yexin Zhang ◽  
Xiaohui He ◽  
Shuai Wang ◽  
Shuchao Pang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Gene Promoter ◽  
Nucleotide Polymorphisms ◽  
Lysosomal Hydrolases ◽  
Mobility Shift ◽  
Regulatory Variants ◽  
Gene Regulatory ◽  
Mobility Shift Assay

Autophagy is involved in many physiological processes. Transcription factor EB (TFEB) is a master regulator of autophagy and coordinates the expression of autophagic proteins, lysosomal hydrolases, and lysosomal membrane proteins. Though autophagy has been implicated in several human diseases, little is known regarding TFEB gene expression and regulation in the process. Since dysfunctional autophagy plays critical roles in acute myocardial infarction (AMI), dysregulated TFEB gene expression may be associated with AMI by regulating autophagy. In this study, the TFEB gene promoter was genetically and functionally analyzed in AMI patients (n = 352) and ethnic-matched controls (n = 337). A total of fifteen regulatory variants of the TFEB gene, including eight single-nucleotide polymorphisms (SNPs), were identified in this population. Among these, six regulatory variants [g.41737274T>C (rs533895008), g.41737144A>G, g.41736987C > T (rs760293138), g.41736806C > T (rs748537297), g.41736635T > C (rs975050638), and g.41736544C > T] were only identified in AMI patients. These regulatory variants significantly altered the transcriptional activity of the TFEB gene promoter. Further electrophoretic mobility shift assay revealed that three of the variants evidently affected the binding of transcription factors. Therefore, this study identified novel TFEB gene regulatory variants which affect the gene expression. These TFEB gene regulatory variants may contribute to AMI development as a rare risk factor.

scholarly journals Functional Genetic Variant in ATG5 Gene Promoter in Acute Myocardial Infarction

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yexin Zhang ◽  
Xiaohui He ◽  
Jiarui Li ◽  
Wentao Yang ◽  
Yinghua Cui ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Genetic Variants ◽  
Transcriptional Activity ◽  
Genetic Variant ◽  
Core Protein ◽  
Gene Promoter ◽  
Mobility Shift ◽  
Hek 293 ◽  
Deletion Variant

Coronary artery disease (CAD) including acute myocardial infarction (AMI) is an inflammatory and metabolic disease mainly caused by atherosclerosis. Dysfunctional autophagy has been associated with abnormal lipid metabolism and inflammation. In previous studies, we have reported altered autophagic activity in AMI patients. As autophagy-related protein 5 (ATG5) is a core protein in autophagy, we speculated that altered ATG5 level may contribute to CAD and AMI development. In this study, the promoter of the ATG5 gene was genetically and functionally investigated in large groups of AMI patients (n = 378) and ethnic-matched healthy controls (n = 386). The results showed that a total of 15 genetic variants including 6 single-nucleotide polymorphisms (SNPs) in the ATG5 gene promoter were found in this study population. A novel deletion variant (g.106326168_70delTCT) and an SNP [g.106325757C > G (rs190825454)] were found in one 66-year-old male patient with non-ST-segment elevated AMI, but in none of controls. In cultured HEK-293 and H9c2 cells, the deletion variant significantly decreased the transcriptional activity of the ATG5 gene promoter (P<0.01). In contrast, the genetic variants either identified only in controls or found in both AMI patients and controls did not affect the transcriptional activity of the ATG5 gene promoter (P>0.05). Furthermore, an electrophoretic mobility shift assay showed that the deletion variant evidently affected the binding of a transcription factor. Therefore, the genetic variant identified in AMI may affect the activity of the ATG5 gene promoter and change the ATG5 level, contributing to AMI as a rare risk factor.

scholarly journals Genetic variants of VEGFR-1 gene promoter in acute myocardial infarction

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Haihua Wang ◽  
Shufang Zhang ◽  
Na Wang ◽  
Jie Zhang ◽  
Mingkai Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Genetic Variants ◽  
Intracellular Signaling ◽  
Transcriptional Activity ◽  
Complex Disease ◽  
Cardiac Fibrosis ◽  
Gene Promoter ◽  
Common Complex Disease ◽  
Mobility Shift

Abstract Background Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis. Vascular epithelial growth factor receptor-1 (VEGFR-1) stimulates angiogenesis and vascular permeability, and functions as a decoy to sequester VEGF and prevent initiation of intracellular signaling. VEGFR-1 knockout mice exhibit significantly higher mortality due to heart failure, cardiac hypertrophy, and cardiac dysfunction. An evident increase in macrophage infiltration and cardiac fibrosis are also observed after transverse aortic constriction. Therefore, VEGFR-1 gene variants may be involved in CAD. In this study, VEGFR-1 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients and ethnic-matched controls. Results A total of 16 DNA sequence variants (DSVs) including six single-nucleotide polymorphisms (SNPs) were found in the VEGFR-1 gene promoter and 5′-untranslated region. Five novel DSVs and one SNP were only identified in AMI patients group. These DSVs and SNP significantly altered the transcriptional activity of the VEGFR-1 gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay indicated that the DSVs and SNPs evidently affected the binding of transcription factors. Conclusions The genetic variants in VEGFR-1 gene identified in AMI patients may alter the transcriptional activity of the VEGFR-1 gene promoter and change VEGFR-1 level, contributing to AMI development.

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study

2019 ◽  
pp. 204748731989467 ◽  
Author(s):  
Liu Miao ◽  
Guo-Xiong Deng ◽  
Rui-Xing Yin ◽  
Rong-Jun Nie ◽  
Shuo Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Plasma Homocysteine ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Artery Disease

Background Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction. Methods A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” ( n = 184,305) and “acute myocardial infarction” ( n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10–8, were used as an instrumental variable. Results None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction ( p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy ( p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction. Conclusions The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

CARDIOVASCULAR PATHOLOGY AS AN IMPORTANT SOCIAL PROBLEM IN PATIENTS WITH CKD

2020 ◽  
Vol 86 (1) ◽  
pp. 58-64
Author(s):  
N. M. Andonieva ◽  
E. A. Huts ◽  
М. Ya. Dubovik ◽  
S. A. Olyanich ◽  
L. V. Mykhailiuk
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Peritoneal Dialysis ◽  
Lipid Metabolism ◽  
Renal Replacement Therapy ◽  
C Reactive Protein ◽  
Reactive Protein

A study of 114 patients who received renal replacement therapy by peritoneal dialysis, whose average age was (47.9±1.2) years, the duration of dialysis therapy - (53.0±2.3) months. EchoCG results with Doppler, bicycle ergometric loading ECG tests are analyzed in dynamics. Depending on the detected changes, patients were divided into five clinical groups. The first group included patients who suffered an acute myocardial infarction during the study. To the second - patients with stable angina. To the third - patients with painless myocardial ischemia. The fourth group included patients with ischemic dilated cardiomyopathy (IDCMP). Fifth - the comparison group, which included patients without signs of coronary heart disease. Patients were determined biochemical parameters of phosphorus-calcium, lipid metabolism, proinflammatory interleukins (TNF-a, IL-1ß, IL-8), C-reactive protein and CAA protein. It was found that cardiorenal syndrome in patients with chronic kidney disease on peritoneal dialysis leads to the progression of coronary heart disease. The formation of different clinical variants of coronary heart disease in such patients is multifactorial, initiated by impaired lipid metabolism with subsequent immunological changes in combination with the processes of remodeling of the left ventricular myocardium, calcification and fibrosis of the aorta, cardiac structures and heart valves. Proinflammatory interleukins TNF-a, IL-1ß, and C-reactive protein are most likely predictors of acute myocardial infarction, whereas IL-8 and acute inflammatory protein (serum amyloid) are associated with ischemic dilated cardiomyopathy, in patients with chronic kidney disease on peritoneal dialysis. Keywords: renocardial syndrome, renal replacement therapy, peritoneal dialysis, coronary heart disease, heart failure.

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