Yongyan Hu1, Laiyuan Wang, Shufeng Chen, Xuehui Liu, Hongfan Li, Xiangfeng Lu, Xueli Yang, Jianfeng Huang, Dongfeng Gu. 1. 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.
Abstract
AIM: 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.
AIM: 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.