Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction
BackgroundAcute myocardial infarction (AMI), a common complex disease caused by an interaction between genetic and environmental factors, is a serious type of coronary artery disease and is also a leading cause of death worldwide. Autophagy-related 16-like 1 (ATG16L1) is a key regulatory factor of a...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.591954/full |
| _version_ | 1818613495709564928 |
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| author | Falan Han Shuchao Pang Zhaoqing Sun Yinghua Cui Bo Yan Bo Yan Bo Yan |
| author_facet | Falan Han Shuchao Pang Zhaoqing Sun Yinghua Cui Bo Yan Bo Yan Bo Yan |
| author_sort | Falan Han |
| collection | DOAJ |
| description | BackgroundAcute myocardial infarction (AMI), a common complex disease caused by an interaction between genetic and environmental factors, is a serious type of coronary artery disease and is also a leading cause of death worldwide. Autophagy-related 16-like 1 (ATG16L1) is a key regulatory factor of autophagy and plays an important role in induced autophagy. In the cardiovascular system, autophagy is essential to preserve the homeostasis and function of the heart and blood vessels. No studies have hitherto examined the association between AMI and ATG16L1 gene promoter.MethodsWe conducted a case-control study, using polymerase chain reaction and sequencing techniques, dual luciferase reporter assay, and electrophoretic mobility shift assay, to analyze genetic and functional variation in the ATG16L1 gene promoter between AMI and controls. A variety of statistical analyses were used to analyze the allele and genotype frequencies and the relationship between single-nucleotide polymorphisms (SNPs) and AMI.ResultsIn all, 10 SNPs and two DNA-sequence variants (DSVs) were identified in 688 subjects, and three ATG16L1 gene promoter mutations [g.233250693 T > C (rs185213911), g.233250946 G > A (rs568956599), g.233251133 C > G (rs1301744254)] that were identified in AMI patients significantly altered the transcriptional activity of ATG16L1 gene promoter in HEH2, HEK-293, and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assays indicated that the SNPs affected the binding of transcription factors (P < 0.01).ConclusionATG16L1 gene promoter mutations in AMI patients may affect the binding of transcription factors and change the transcriptional activity of the ATG16L1 gene, changing the level of autophagy and contributing to the occurrence and development of AMI as rare and low-frequency risk factors. |
| first_indexed | 2024-12-16T16:03:02Z |
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| id | doaj.art-291b213eb1b54c23bf1dc1595444d813 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-16T16:03:02Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-291b213eb1b54c23bf1dc1595444d8132022-12-21T22:25:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-06-011210.3389/fgene.2021.591954591954Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial InfarctionFalan Han0Shuchao Pang1Zhaoqing Sun2Yinghua Cui3Bo Yan4Bo Yan5Bo Yan6Cheeloo College of Medicine, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, ChinaCheeloo College of Medicine, Shandong University, Jinan, ChinaDivision of Cardiology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, ChinaShandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, ChinaThe Center for Molecular Genetics of Cardiovascular Diseases, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, ChinaShandong Provincial Sino-US Cooperation Research Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, ChinaBackgroundAcute myocardial infarction (AMI), a common complex disease caused by an interaction between genetic and environmental factors, is a serious type of coronary artery disease and is also a leading cause of death worldwide. Autophagy-related 16-like 1 (ATG16L1) is a key regulatory factor of autophagy and plays an important role in induced autophagy. In the cardiovascular system, autophagy is essential to preserve the homeostasis and function of the heart and blood vessels. No studies have hitherto examined the association between AMI and ATG16L1 gene promoter.MethodsWe conducted a case-control study, using polymerase chain reaction and sequencing techniques, dual luciferase reporter assay, and electrophoretic mobility shift assay, to analyze genetic and functional variation in the ATG16L1 gene promoter between AMI and controls. A variety of statistical analyses were used to analyze the allele and genotype frequencies and the relationship between single-nucleotide polymorphisms (SNPs) and AMI.ResultsIn all, 10 SNPs and two DNA-sequence variants (DSVs) were identified in 688 subjects, and three ATG16L1 gene promoter mutations [g.233250693 T > C (rs185213911), g.233250946 G > A (rs568956599), g.233251133 C > G (rs1301744254)] that were identified in AMI patients significantly altered the transcriptional activity of ATG16L1 gene promoter in HEH2, HEK-293, and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assays indicated that the SNPs affected the binding of transcription factors (P < 0.01).ConclusionATG16L1 gene promoter mutations in AMI patients may affect the binding of transcription factors and change the transcriptional activity of the ATG16L1 gene, changing the level of autophagy and contributing to the occurrence and development of AMI as rare and low-frequency risk factors.https://www.frontiersin.org/articles/10.3389/fgene.2021.591954/fullacute myocardial infarctionATG16L1gene promotersingle-nucleotide polymorphismsautophagy |
| spellingShingle | Falan Han Shuchao Pang Zhaoqing Sun Yinghua Cui Bo Yan Bo Yan Bo Yan Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction Frontiers in Genetics acute myocardial infarction ATG16L1 gene promoter single-nucleotide polymorphisms autophagy |
| title | Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction |
| title_full | Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction |
| title_fullStr | Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction |
| title_full_unstemmed | Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction |
| title_short | Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction |
| title_sort | genetic variants and functional analyses of the atg16l1 gene promoter in acute myocardial infarction |
| topic | acute myocardial infarction ATG16L1 gene promoter single-nucleotide polymorphisms autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.591954/full |
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