Functional variants in the LC3B gene promoter in acute myocardial infarction.
J Cell Biochem
; 119(9): 7339-7349, 2018 09.
Article
in En
| MEDLINE
| ID: mdl-29761913
ABSTRACT
Acute myocardial infarction (AMI) is a common disease mainly caused by atherosclerosis, for which genetic causes remain largely unknown. Recently, low frequency and rare genetic variants have been proposed as risk factors. Autophagy has been involved in many cellular processes, such as lipid metabolism and inflammation, and implicated in human diseases, including cardiovascular diseases. In previous studies, we have reported reduced levels of LC3B, a core protein and a marker for autophagy, in AMI patients. In this study, the LC3B gene promoter was genetically and functionally analyzed in large cohorts of AMI patients (n = 383) and healthy controls (n = 390). A total of 25 DNA sequence variants (DSVs) including SNPs were found. Seven DSVs and three SNPs were only identified in AMI patients. All the DSVs and SNPs (except one) significantly decreased the transcriptional activity of the LC3B gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay suggested that the DSVs affected the binding of transcription factors. In contrast, the DSVs and SNPs found only in controls or in both AMI patients and controls did not significantly affected LC3B gene promoter activity (P > 0.05). Therefore, our data suggested that the DSVs identified in AMI patients may change LC3B level by affecting the transcriptional activity of LC3B gene promoter, contributing to the AMI development. Upregulation of the LC3B gene expression may provide a novel and potential therapy for AMI patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coronary Artery Disease
/
Base Sequence
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Promoter Regions, Genetic
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Polymorphism, Single Nucleotide
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Microtubule-Associated Proteins
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Myocardial Infarction
Type of study:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
J Cell Biochem
Year:
2018
Document type:
Article
Affiliation country: