AUTHOR=Han Falan , Pang Shuchao , Sun Zhaoqing , Cui Yinghua , Yan Bo 

TITLE=Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.591954

DOI=10.3389/fgene.2021.591954

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Acute 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 (<italic>ATG16L1</italic>) 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 <italic>ATG16L1</italic> gene promoter.</p></sec><sec><title>Methods</title><p>We 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 <italic>ATG16L1</italic> 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.</p></sec><sec><title>Results</title><p>In all, 10 SNPs and two DNA-sequence variants (DSVs) were identified in 688 subjects, and three <italic>ATG16L1</italic> gene promoter mutations [g.233250693 T &gt; C (rs185213911), g.233250946 G &gt; A (rs568956599), g.233251133 C &gt; G (rs1301744254)] that were identified in AMI patients significantly altered the transcriptional activity of <italic>ATG16L1</italic> gene promoter in HEH2, HEK-293, and H9c2 cells (<italic>P</italic> &lt; 0.05). Further electrophoretic mobility shift assays indicated that the SNPs affected the binding of transcription factors (<italic>P</italic> &lt; 0.01).</p></sec><sec><title>Conclusion</title><p><italic>ATG16L1</italic> gene promoter mutations in AMI patients may affect the binding of transcription factors and change the transcriptional activity of the <italic>ATG16L1</italic> gene, changing the level of autophagy and contributing to the occurrence and development of AMI as rare and low-frequency risk factors.</p></sec>