CELSR2基因启动子区甲基化与代谢综合征痰证的关系研究

Relationship Between CELSR2 Gene Promoter Methylation and Phlegm Syndrome of Metabolic Syndrome

目的 检测代谢综合征(MS)痰证、非痰证患者及健康人外周血中CELSR2基因CpG位点DNA甲基化水平,初步探索MS痰证形成的表观遗传学机制。方法 收集MS患者,运用证素辨证法筛选MS痰证、非痰证患者各27例,并以27名健康人为对照。理化指标检测包括:收缩压(SBP)、舒张压(DBP)、身体重指数(BMI)、腰围(WC)、空腹血糖(FPG)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C);MethylTarget方法检测CELSR2基因启动子区41个CpG位点的DNA甲基化水平。结果 与健康组比较,MS痰证、非痰证组中SBP、DBP、BMI、WC、FPG、TG升高而HDL-C降低(P<0.01);与MS非痰证组比较,MS痰证组中DBP、BMI、WC、FPG、TG升高(P<0.05)。与健康组比较,MS非痰证组中CpG28、CpG34 DNA甲基化水平降低(P<0.05),MS痰证组中CpG24、CpG34 DNA甲基化水平降低(P<0.05);与MS非痰证组比较,痰证组中CpG20、CpG24、CpG34 DNA甲基化水平降低(P<0.01)。与健康组比较,MS患者吸烟、饮酒人数较多(P<0.01);与MS非痰证组比较,痰证组饮酒人数增多(P<0.05)。与CELSR2基因CpG34甲基化率正常比较,低甲基化发生MS痰证的风险是其4.14倍(95%CI:1.25~13.70,P<0.05);与未饮酒相比,饮酒发生MS痰证的风险是其3.55倍(95%CI:1.07~11.82,P<0.05)。结论 DBP、BMI、WC、FPG、TG升高可能使MS痰证形成的风险升高,CELSR2基因CpG34位点的DNA低甲基化可能是MS痰证形成的表观遗传学基础,饮酒是MS痰证形成的危险因素。

Objective To detect the DNA methylation level of CpG sites in CELSR2 gene promoter region in patients with phlegm syndrome, non-phlegm syndrome of metabolic syndrome(MS) and healthy people,and to explore the epigenetic mechanism of phlegm syndrome of MS. Methods MS patients were collected,and 27 patients with phlegm syndrome and 27 patients without phlegm syndrome were screened by syndrome differentiation method,and 27 healthy people were selected as healthy group. Physicochemical indexes were detected,including systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),waist circumference(WC),fasting plasma glucose(FPG),triglyceride(TG),high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C).The DNA methylation level of 41 CpG sites in the promoter region of CELSR2 gene was detected by MethylTarget method. Results Compared with the healthy group,the SBP,DBP,BMI,WC,FPG and TG increased and the HDL-C decreased in phlegm syndrome and non-phlegm syndrome group(P<0.01). Compared with the non-phlegm syndrome group,the DBP,BMI,WC,FPG and TG increased in phlegm syndrome group(P<0.05). Compared with the healthy group,the DNA methylation levels of CpG28 and CpG34 in the non-phlegm syndrome group decreased(P<0.05),and the DNA methylation levels of CpG24 and CpG34 in the phlegm syndrome group decreased(P<0.05).Compared with the non-phlegm syndrome group,the DNA methylation levels of CpG20,CpG24 and CpG34 in the phlegm syndrome group decreased(P<0.01). Compared with the healthy group,the number of smoking and drinking in MS patients was higher(P<0.01).Compared with the non-phlegm syndrome group,the number of drinkers in the phlegm syndrome group increased(P<0.05).Compared with the normal methylation rate of CELSR2 gene CpG34,the risk of MS phlegm syndrome with low methylation was 4.14 times(95%CI:1.25-13.70,P<0.05). Compared with no drinking,the risk of MS phlegm syndrome with drinking was 3.55 times(95%CI:1.07-11.82,P<0.05). Conclusions The increase of DBP,BMI,WC,FPG,TG may increase the risk of MS phlegm syndrome. The DNA hypomethylation of CELSR2 gene CpG34 locus may be the epigenetic basis of MS phlegm syndrome. Drinking is a risk factor for the formation of MS phlegm syndrome.