Two tagSNPs rs352493 and rs3760908 within<i>SIRT6</i>Gene Are Associated with the Severity of Coronary Artery Disease in a Chinese Han Population

Tang, Sai-sai; Xu, Shun; Cheng, Jie; Cai, Meiying; Chen, Lin; Liang, Lili; Yang, Xia; Chen, Can; Liu, Xinguang; Xiong, Xing‐Dong

doi:10.1155/2016/1628041

Cited by 9 publications

(9 citation statements)

References 38 publications

(34 reference statements)

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“…However, they have no clinical significance since they almost remain within the normal range (TC: 2.8–5.17 mmol/L, LDL-C: 0–3.1 mmol/L). Many researchers have investigated the association between the gene polymorphism of candidate genes and the severity of CAD that was defined by the number of vessels with significant stenosis [14,24]. No association was found between two SNPs of miR-146a and the severity of CAD in our study.…”

Section: Discussioncontrasting

confidence: 66%

“…The diagnosis of CAD was confirmed by coronary angiography (CA). The diagnostic criteria is at least one major epicardial coronary artery shows more than 50% organic stenosis [ 14 ]. The controls were defined to be free of CAD by CA, and assistant diagnoses such as electrocardiograms, clinical examinations, and medical histories were also performed.…”

Section: Methodsmentioning

confidence: 99%

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Two Single Nucleotide Polymorphisms (rs2431697 and rs2910164) of miR-146a Are Associated with Risk of Coronary Artery Disease

Wang

et al. 2017

IJERPH

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The coronary artery disease (CAD) is one of the most severe cardiovascular diseases. MicroRNA-146a (miR-146a) influences the pathology of cardiovascular diseases. Two single nucleotide polymorphisms (SNPs) of miR-146a (rs2431697 and rs2910164) have been reported to alter the function or expression of microRNA. The purpose of this study is to evaluate the association between miR-146a gene polymorphism and the risk of CAD in the Chinese population. A total of 353 CAD patients and 368 controls were recruited, and SNPs were analyzed by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and Sequenom MassARRAY system. The gene frequencies of rs2431697 and rs2910164 were significantly different between the two groups. The mutant type (T allele) of rs2431697 and wild type (C allele) of rs2910164 were more frequent in CAD patients. T allele carriers in rs2431697 had an increased CAD risk, while G allele of rs2910164 decreased the risk of CAD significantly. In conclusion, we found that the T allele of rs2431697 was a risk factor of CAD in the Chinese population. Meanwhile, we demonstrated that the G allele of rs2910164 decreased the susceptibility of CAD.

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Section: Discussioncontrasting

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Two Single Nucleotide Polymorphisms (rs2431697 and rs2910164) of miR-146a Are Associated with Risk of Coronary Artery Disease

Wang

et al. 2017

IJERPH

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“…More recently, SIRT6 expression was reported to decrease in atherosclerotic ApoE −/− mice [ 26 , 27 ] and human patients [ 23 , 27 ]. Moreover, SIRT6 genetic variants (rs107251, rs352493 and rs3760908) have been reported to associate with severity of coronary artery disease (CAD) [ 28 , 29 ]. Therefore, further understanding of the atheroprotective role of SIRT6 would facilitate the translational exploitation of SIRT6 based therapeutic approaches in treating CAD.…”

Section: Introductionmentioning

confidence: 99%

SIRT6 protects against endothelial dysfunction and atherosclerosis in mice

Yin

Koroleva

et al. 2016

Aging

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SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE−/− mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation. Moreover, SIRT6+/− haploinsufficient mice fed a high-fat diet (HFD) also displayed impaired endothelium-dependent vasorelaxation. Importantly, SIRT6+/−;ApoE−/− mice after HFD feeding exhibited exacerbated atherosclerotic lesion development, concurrent with increased expression of the proinflammatory cytokine VCAM-1. Loss- and gain-of-SIRT6 function studies in cultured human endothelial cells (ECs) showed that SIRT6 attenuated monocyte adhesion to ECs. RNA-sequencing profiling revealed that SIRT6 overexpression decreased the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4). Chromatin immunoprecipitation assays showed that SIRT6 decreased TNFSF4 gene expression by binding to and deacetylating H3K9 at TNFSF4 gene promoter. Collectively, these findings demonstrate that SIRT6 play a pivotal role in maintaining endothelial function and increased SIRT6 activity could be a new therapeutic strategy to combat atherosclerotic disease.

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“…Atherosclerosis can lead to organ disease ( 15 ). Occurrence of coronary heart disease may be related to dyslipidemia, genetic, environmental and other factors ( 16 , 17 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of irbesartan combined with atorvastatin calcium in the treatment of rats with coronary heart disease

Yao²

2018

Exp Ther Med

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This study aimed to investigate the therapeutic effect of irbesartan combined with atorvastatin calcium in the treatment of rats with coronary heart disease. One hundred sixty Wistar rats were selected to establish coronary heart disease model. Rats with coronary heart disease were randomly divided into 4 groups: Model, irbesartan, atorvastatin calcium and combination groups (irbesartan combined with atorvastatin calcium group). Rats in irbesartan group were treated with 50 mg/(kg.day) irbesartan; rats in atorvastatin calcium group were given atorvastatin calcium at a dose of 10 mg/(kg.day); rats in combination group were subjected to atorvastatin calcium at a dose of 10 mg/(kg.day) and irbesartan at a dose of 50 mg/(kg.day), while rats in model groups were given intragastric administration of normal saline at a dose of 2 ml/day. Serum lipids, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and TC/HDL-C, were measured by automatic biochemical analyzer. Expression of sPLA2-V in myocardium and aortic trunk of rats was detected by reverse transcription-PCR (RT-PCR) and western blot analysis. After treatment, levels of serum TC, TG, LDL-C, HDL-C and TC/HDL-C in rats of each treatment group were better than those in model group (p<0.05). Expression level of sPLA2-V in myocardium and aortic trunk in model group was significantly higher than that in other groups (p<0.05). Expression level of sPLA2-V in combination group was significantly lower than that in irbesartan and atorvastatin calcium groups (p<0.05). Combination of irbesartan and atorvastatin calcium is superior to irbesartan or atorvastatin calcium alone in the treatment of rats with coronary heart disease. The possible explanation is that the two drugs can reduce the expression of sPLA2-V in myocardium and aortic trunk, which in turn relieved atherosclerosis and achieved better therapeutic effect.

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Two tagSNPs rs352493 and rs3760908 withinSIRT6Gene Are Associated with the Severity of Coronary Artery Disease in a Chinese Han Population

Cited by 9 publications

References 38 publications

Two Single Nucleotide Polymorphisms (rs2431697 and rs2910164) of miR-146a Are Associated with Risk of Coronary Artery Disease

Two Single Nucleotide Polymorphisms (rs2431697 and rs2910164) of miR-146a Are Associated with Risk of Coronary Artery Disease

SIRT6 protects against endothelial dysfunction and atherosclerosis in mice

Therapeutic effect of irbesartan combined with atorvastatin calcium in the treatment of rats with coronary heart disease

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