Research of aberrant global DNA methylation level in CD14+ monocytes in patients with coronary artery disease and its mechanism
10.13699/j.cnki.1001-6821.2017.18.002
- VernacularTitle:冠心病患者CD14+单核细胞总体DNA异常甲基化及其机制研究
- Author:
Ke-Qin GAO
1
;
Su-Jie JIA
Author Information
1. 中南大学湘雅三医院药学部
- Keywords:
atherosclerosis;
monocytes;
genomic DNA global methylation;
DNA methyltransferases;
methyl binding protein 2
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(18):1740-1743
- CountryChina
- Language:Chinese
-
Abstract:
Objective To research mainly focuses on the changes of genomic DNA global methylation of peripheral blood CD14 + monocytes in patients with coronary artery disease (CAD).Methods CD14 + monocytes were isolated from peripheral blood of treatment group (CAD patients) and control group(no-CAD patients) by density gradient centrifugation and magnetic bead selection.We detected genomic DNA global methylation level with genome global methylation quantitation kit.Quantitive real-time polymerase chain reaction(qRT-PCR) was performed to detect the expression levels of DNA methyltransferases (DNMTs) and methyl binding protein 2 (MBD2) mRNA.Results In control group and treatment group,genomic DNA global methylation levels of CD14 + monocytes were 0.30 ± 0.04,0.44 ± 0.03,the difference was statistically significant(P < 0.05).In control group and treatment group,the expression levels of DNMT1 mRNA were 2.16 ± 0.32,1.40 ± 0.13,with significant difference(P <0.05).The expression levels of DNMT3A mRNA were 0.56 ± 0.05,0.89 ±0.12,with significant difference(P <0.05).The expression levels of DNMT3B mRNA were 0.59 ±0.07,0.97 ±0.10,with significant difference(P <0.01).The expression levels of MBD2 mRNA were 1.68 ±0.20,1.20 ±0.08,with significant difference(P <0.01).In treatment group of coronary heart disease,global methylation level and the expression levels of DNMT1 mRNA (r =0.648) as well as DNMT3B (r =0.700) were positive correlated and statistically significant (both P < 0.05),global methylation level and the expression levels of MBD2 (r =-0.540) were negative correlated and statistically significant(P <0.05),while global methylation level and the expression level of DNMT3A were not correlated,the difference was not significant (P > 0.05).Conclusion Genomic DNA of peripheral CD14 + monocytes in patients with coronary artery disease presents global hypermethylation,which may be as a result of out-of-balance between methylation and demethylation induced by abnormal expressions of DNMTs and MBD2.