Correlation Between ApoE Gene Polymorphism And MiRNA-33/223 Level In Patients With Coronary Heart Disease

Background: The occurrence of coronary artery disease（CAD）is determined by environmental factors and genetic factors,and the genetic factors are usually in a complex pattern.Micrornas（miRNA）are key regulators involved in Lipid metabolism and the development of CAD.Recent studies have shown that ApoE genes also play an important role in the regulation of Lipid Metabolism and influence the development of CAD,but little has been reported about whether the re is a link.Therefore,to investigate the relationship between ApoE polymorphis m and circulating miRNA-33/223 levels in patients with CAD,and to determine if there is a relationship between ApoE and miRNA-33/223 levels,so as to provide more scientific evidence for early diagnosis,treatment and prevention of CAD.Objective: To explore the correlation between the three allelic loci（ApoE2,ApoE3,ApoE4） in the ApoE gene and the expression levels of miRNA-33 and miRNA-223,as well as the influence of ApoE genetic polymorphisms on blood lipid levels to guide Individualized lipid-lowering therapy for patients with CAD.Methods: From January 2020 to December 2020,a total of 208 inpatients with CAD diagnosed by coronary arteriography were selected from Dongfeng General Hospital of Chinese traditional medicine.All of them were given the same dosage and the same Rosuvastatin every night,among them,108 cases were male and 100 cases were female.The basic data of the patients were collected and the biochemical indexes were measured in the Laboratory Department of the hospital.The basic data of the patients were collected and the biochemical indexes were determined in the laboratory department of the hospital.The ApoE gene polymorphism and the expression of serum miRNA-33/223 in all samples were detected by real-time fluorescence quantitative PCR.The research subjects were divided into 3 groups according to the genotype,and the E2 phenotype group: the genotype was E2/2+E2/3;E3 phenotype group: genotype E3/3+E2/4;E4 phenoty pegroup: genotype E3/4+E4/4.The relationship between ApoE gene polymorphism and miRNA-33/223 content and the correlation between ApoE gene polymorphism and blood lipid were compared among the three groups.Results: 1.The comparison of ApoE genotypes showed that there was no significant difference in general clinical basic data,age,gender,course of disease,smoking history,drinking history,blood pressure,BMI,Cr,FBG,BUN,UA,ALT and AST among E2 group,E3 group and E4 group（P > 0.05）.2.There were significant differences in blood lipid levels among the three groups,total cholesterol（TC）and low-density lipoprotein cholesterol（LDL-C）: E4group>E3 group>E2 group,the difference was statistically significant（F=TC11.992 P <0.001;F=7.938 P<0.001）,and there were statistical differences among the three groups（P<0.05）.（2）Triglyceride（TG）: E4 group>E3 group>E2 group,the difference was statistically significant（F=3.623 P=0.028）,but there was no significant difference between E2 group and E3 group,（P =0.278）,and there were statistically significant differences between E3 and E4 groups,and E2 and E4 groups （P<0.05）.（3）High-density lipoprotein cholesterol（HDL-C）: E2 group>E3 group>E4 group,but the difference was not statistically significant（F=1.257 P=0.286）.3.The relationship between ApoE gene polymorphism and miRNA-33/223 content,miRNA-33: E4 group>E3 group>E2 group,the difference was statistically significant（F=3.321,P=0.039）;miRNA-223: E2 Group>E3>E4,the difference w as statistically significant（F=7.767,P=0.001）.Conclusion: In the same CAD patient,there was a correlation between ApoE gene polymorphism and the levels of miRNA-33 and miRNA-223 in circulatin g blood,and the levels of TC,LDL-C and miRNA-33 were higher in patients with E4 allele,E4 allele and high levels of miRNA-33 may jointly affect the progression of CAD by regulating lipid metabolism.When the E2 allele exists,the levels of TC and LDL-C are lower,and the level of miRNA-223 is higher.The parallel of the E2 allele and the high level of miRNA-223 may promote the efficacy of statin by regulating the blood lipid pathway.ApoE gene polymorphism may affect the efficacy of statin lipid-lowering drugs.Patients with E2 allele carriers have better control of blood lipids,and the effect of statins in E2 patients is better than that in E4 patients.