The Relationship Between Methylation Level Of ABCA1 Gene Promoter And Coronary Heart Disease

ObjectThis study was designed to investigate the relationship between methylation level of ATP-binding cassette transporter A1（ABCA1）gene promoter and coronary atherosclerotic heart disease（CHD）,to explore candidate genes which possess an important impact on the incidence of CHD in China.Methods1.Fifty patients with coronary heart disease confirmed by coronary angiography（CAG）who were hospitalized in the First Department of Cardiology of Fujian Provincial Hospital during the period from January 2019 to January 2020 were randomly selected as the case group（coronary atherosclerotic heart disease group）,and30 patients who visited our hospital during the same period and were excluded from CHD by CAG or coronary CT angiography（CTA）were included in the control group（normal group）.Their complete blood samples were collected and DNA was extracted to relatively quantitate the methylation level of the promoter of the target gene by Methylation specific real-time quantitative polymerase chain reaction（q MSP）.2.The general data of patients were collected,including name,sex,age,BMI,drinking history,smoking history,ect.Fasting blood glucose（FBG）,high-density lipoprotein cholesterol（HDL-C）,total cholesterol（TC）and triglyceride（TG）and other related indicators were measured by the laboratory department of our hospital.3.The methylation level of DNA was assessed by methylation index.MI=M/（M+U）*100%,M/U=2^-△Ct,△Ct=methylated Ct _ABCA1-unmethylated Ct _ABCA1.Results1.Smoking rate,drinking rate,hypertension,diabetes,glycosylated hemoglobin,fasting blood glucose,HDL-C and ApoA were significant differences in the two groups.Except HDL-C and ApoA,the CHD group was higher than the normal group.2.The methylation level of ABCA1 gene promoter region in（CHD）group was significantly higher than that in normal group（P<0.05）.Gender stratification analysis showed that the methylation level of ABCA1 gene promoter region in both male and female population was higher than that in normal group,and there was statistical significance in female group（P<0.05）,but not in male group.Age stratification analysis showed that the methylation level of ABCA1 gene promoter region in the CHD group was higher than that in the normal group,and there was significant difference in the age<65 years old group（P<0.05）,but not in the age≥65 years old group.3.The methylation level of ABCA1 gene promoter was a risk factor for CHD（OR=1.087,95%CI:1.010～1.170）,but it was not an independent risk factor CHD.4.The methylation level of ABCA1 promoter in peripheral blood was positively correlated with the level of ApoB（rs=0.249,P<0.05）.In patients with CHD,the level of ABCA1 methylation was positively correlated with the levels of TC,LDL-C and ApoB（TC,rs=0.294,P<0.05;LDL-C,rs=0.284,P<0.05;ApoB,rs=0.365,P<0.01）.In male CHD patients,the level of ABCA1 methylation was positively correlated with the levels of TC,LDL-C and ApoB（TC,rs=0.341,P<0.05;LDL-C,rs=0.325,P<0.05;ApoB,rs=0.398,P=0.01）,and ABCA1 methylation level was positively correlated with TG level in female CHD patients（TG,rs=0.845,P<0.01）.In patients with<65 years old CHD,the level of ABCA1 methylation was positively correlated with the level of TG（TG,rs=0.430,P<0.05）.In patients with CHD≧65 years old,the level of ABCA1methylation was positively correlated with the level of ApoB（ApoB,rs=0.393,P<0.05）.5.There was a positive correlation between age and methylation level in the promoter region of ABCA1 gene（rs=0.297,P<0.01）,especially in female patients with CHD（rs=0.803,P<0.05）.6.The methylation level of ABCA1 promoter region was positively correlated with Gensini score in patients with CHD（rs=0.311,P<0.05）.Conclusions1.Hypermethylation in the promoter region of ABCA1 gene is associated with high ApoB concentration and CHD.Besides,it is a risk factor for CHD.2.Age is associated with hypermethylation in the promoter region of ABCA1.There is a gender difference in the relationship between hypermethylation in the promoter region of ABCA1 gene and CHD,which is significant in women.3.The methylation level of ABCA1 gene promoter is positively correlated with the severity of coronary artery disease in patients with CHD.