title: Association between the SIRT1 mRNA expression and acute coronary syndrome.
abstract: OBJECTIVE
  Silent mating type information regulator 2 homolog 1 (SIRT1) functions as an atheroprotective factor in vascular biology, and genetic variations in SIRT1 are associated with coronary artery calcification and type 2 diabetes in several populations. In this study, we investigated the relationship between the mRNA expression levels of the SIRT1 gene and single nucleotide polymorphisms (SNPs) in the context of acute coronary syndrome (ACS).
  
  
  METHODS
  Whole-genome expression microarray and real-time PCR techniques were used to detect the gene expression levels, and Western blotting was performed to determine the protein expression level. The four selected SNPs were genotyped in a Taqman genotyping platform.
  
  
  RESULTS
  Compared with that observed in the controls, the mRNA expression levels of the SIRT1 gene in the microarray study were significantly lower in the acute myocardial infarction (AMI), unstable angina (UA) and overall ACS patients. These results were replicated in another independent cohort with respect to the mRNA (AMI, p＜0.001; UA, p＜0.001; ACS, p＜0.001) and protein (p＜0.05) levels. Furthermore, the relationship between the SIRT1 mRNA expression and the genotypes of four possible functional SNPs (rs12778366, rs3758391, rs2273773 and rs4746720) was tested, the results of which showed significant differences in the SIRT1 mRNA expression among the allelic genes of rs3758391 (p＜0.01) in the healthy participants.
  
  
  CONCLUSIONS
  The present results confirm that the SIRT1 gene plays a protective role against ACS and that the rs3758391 SNP affects the mRNA expression in healthy participants, providing new insight into the processes regulating the genetic control of the SIRT1 gene with respect to the pathogenesis of ACS.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; National Human Genome Center at Beijing, Beijing, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Hu
authors.forename: Laiyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.forename: Xuehui
authors.initials: X
authors.lastname: Liu
authors.forename: Hongfan
authors.initials: H
authors.lastname: Li
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.forename: Xueli
authors.initials: X
authors.lastname: Yang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C447939:SIRT1 protein, human; D056564:Sirtuin 1