Dysregulation Of SIRT7 Gene Expression In Myocardial Infarction

Objective: Coronary artery disease(CAD)is a common and complex cardiovascular disease,which can affect the blood supply of coronary artery,leading to myocardial ischemia,and the,there is the risk of myocardial infarction for patients with CAD,acute myocardial infarction is the severe type of CAD.The incidence of CAD is attributed to the interaction between environmental and genetic factors.In recent years,more and more evidence reveal that the genetic polymorphisms of relevant genes are related to the risk of CAD,according to a genome-wide association study data,more than 50 alleles are associated with CAD,but these mutations can account for only about 10% of the patients with CAD.Therefore,we hypothesize that low frequency and rare variation of genetic may be an important cause of CAD,especially acute myocardial infarction.SIRT7 is a highly conserved NAD+-dependent deacetylase of the sirtuins family,is a key regulator of many cellular events involved in the regulation of many biological processes,including cell proliferation,genomic stability,metabolic balance,stress,aging,tumor occurrence and so on,and it may be involved in the process of malignant tumor,cardiovascular disease,fat liver and diabetes.According to the role of SIRT7 in cardiovascular disease,and the process of regulating cell survival and apoptosis and lipid metabolism,we hypothesize that the DNA sequence variation(DSVs)of SIRT7 gene promoter regulation region will change the expression level of SIRT7 gene,then leading to the occurrence and development of CAD.Methods: We analyze SIRT7 gene promoter genetically in ethnic-matched controls(n=341)and large cohorts of MI patients(n=424).Leukocytes in blood were isolated and DNAs were extracted,the promoter region of SIRT7 gene was generated by PCR and then the objective fragments of DNA were sequenced.According to the sequencing results,we can analyze the DNA sequence variation of SIRT7 gene promoter region.Results: In this study,we found a total of 8 DNA sequence variation,including one single nucleotide polymorphisms(SNPs),one sequence variation of deletion and six sequence variation of single base.Among these,there heterozygous DNA sequence variants(g.81914007T>C,g.81914121C>T,g.81914401A>T)and one heterozygous DNA sequence variants of deletion(g.81914493Del)were found in four AMI patients,and were not found in control group.Conclusion: This study reveals that,in AMI patients,the DNA sequence variants may change the transcriptional activity of SIRT7 gene promoter,and then change the expression level of SIRT7 gene,leading to changes of SIRT7 gene function,as result,the AMI happened and developed.