Format

Send to

Choose Destination
Gene. 2018 Oct 30;675:233-239. doi: 10.1016/j.gene.2018.07.010. Epub 2018 Jul 4.

Functional genetic variants in the SIRT5 gene promoter in acute myocardial infarction.

Author information

1
Center for Molecular Medicine, Yanzhou People's Hospital, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272100, China.
2
Division of Laboratory Medicine, Yanzhou People's Hospital, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272100, China.
3
Department of Medicine, Shandong University School of Medicine, Jinan, Shandong 250012, China.
4
Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
5
Division of Cardiology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
6
Division of Cardiology, Yanzhou People's Hospital, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272100, China. Electronic address: jnmcyan@mail.jnmc.edu.cn.
7
Center for Molecular Medicine, Yanzhou People's Hospital, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272100, China; Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China; The Center for Molecular Genetics of Cardiovascular Disease, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China. Electronic address: yanbo@mail.jnmc.edu.cn.

Abstract

Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease. To date, genetic causes for atherosclerosis remain largely unknown. It has recently been proposed that low frequency and rare genetic variants may be the main causes. Mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, function as critical regulators of mitochondrial metabolism, oxidative stress and cell survival. We speculated that altered SIRT5 level resulting from DNA sequence variants (DSVs) within SIRT5 gene regulatory regions may contribute to the CAD and AMI development. In this study, the SIRT5 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients (n = 381) and healthy controls (n = 391). A total of eleven DSVs and SNPs were found. Two novel heterozygous DSVs (g.13574131C>A and g.13574287G>C) and three heterozygous SNPs [g.13573450A>G (rs573515169), g.13574110G>A (rs2804924) and g.13574259G>C (rs112443954)] were identified only in AMI patients. The DSVs and SNPs significantly decreased the transcriptional activity of the SIRT5 gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay indicated that the SNPs significantly affected the binding of transcription factors. In contrast, the DSVs and SNPs found only in controls or in both AMI patients and controls did not significantly change the SIRT5 gene promoter activity (P > 0.05). Therefore, our data suggested that the DSVs and SNPs identified in AMI patients may change SIRT5 level by affecting activity of SIRT5 gene promoter, contributing to the AMI development as a risk factor.

KEYWORDS:

Acute myocardial infarction; DNA sequence variants; Promoter; SIRT5; SNP

PMID:
29981421
DOI:
10.1016/j.gene.2018.07.010
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center