title: Genetic analysis of the SIRT1 gene promoter in myocardial infarction.
abstract: Myocardial infarction (MI) is a restrictive phenotype of coronary artery disease. To date, a group of genes and genetic loci have been associated to MI. However, the genetic causes and underlying molecular mechanisms for MI remain largely unknown. SIRT1, one of highly conserved NAD-dependent class III deacetylases, has been involved in several cellular processes and implicated in human diseases. Autophagy is one of major cellular degradative pathways, which plays important roles in lipid metabolism. Recent studies have shown that SIRT1 deacetylates autophagy-related genes, and the expressions of autophagic genes are altered in MI patients. Accordingly, we hypothesized that SIRT1 may be linked to the MI pathogenesis. In this study, the SIRT1 gene promoter were genetically analyzed in large cohorts of MI patients (n = 327) and controls (n = 358). The results showed that six single-nucleotide polymorphisms and 14 sequence variants were identified. Among these, five novel heterozygous variants (g.69643743Ins, g.69643840Ins, g.69643903G > C, g.69644235G > C and g.69644353G > T) and one single-nucleotide polymorphism (rs35706870) were identified in MI patients, but in none of controls. Moreover, five novel heterozygous variants (g.69643672G > A, g.69644226C > T, g.69644278A > G, g.69644408G > A and g.69644408G > T) were only found in controls. The rest variants were found in MI patients and controls with similar frequencies. Taken together, the variants identified in MI patients may alter the transcriptional activities of SIRT1 gene promoter, which may change SIRT1 levels, contributing to the MI pathogenesis as a risk factor.
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Cui
authors.forename: Haihua
authors.initials: H
authors.lastname: Wang
authors.forename: Houzao
authors.initials: H
authors.lastname: Chen
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Depei
authors.initials: D
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D056564:Sirtuin 1 / Q000235:genetics*
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1