Study On The Common Environmental Factors Of Coronary Heart Disease And Competing Endogenous RNA Of Specific CircRNA

Objective To explore the main environmental factors of coronary heart disease?CHD?,screen and verify circRNA,miRNA and mRNA differentially expressed in peripheral blood of patients with CHD case and control group,construct CHD related circRNA-miRNA-mRNA competing endogenous RNA network,study the value of peripheral blood circRNA and miRNA expression levels in the diagnosis of CHD,construct an epigenetic risk score for CHD,analysis of the impact of epigenetic risk score and environmental factors on CHD and their potential interactions.Method?1?The hospital-based case-control study was applied.From October 2016 to June 2018,739 cases of CHD patients and 1877 cases of healthy controls were collected in accordance with strict inclusion criteria and exclusion criteria at the First Affiliated Hospital of Fujian Medical University,the Union Hospital of Fujian Medical University and the People's Hospital of Fujian Province.Questionnaires,physical examinations and laboratory tests were conducted on the subjects,and their general demographic characteristics,individual behavioral factors,physiological indicators,psychosocial factors,disease history and family history were collected.Logistic regression model was used to explore the main environmental influencing factors of CHD.?2?High-throughput gene chip technology was used to screen for CHD related circRNA,miRNA and mRNA.CircRNA-miRNA-mRNA competing endogenous RNA networks was constructed by bioinformatics analysis,and differentially expressed circRNA,miRNA and mRNA were verified by qRT-PCR.Logistic regression model was used to investigate whether circRNA and miRNA are independent risk factors for CHD.ROC curve was used to evaluate the value of each index in diagnosing CHD.The joint action of environmental factors and epigenetic factors were analyzed by cross-sectional analysis with logistic regression model.Result?1?Compared with light-intensity occupational physical activity,moderate-intensity occupational activity and heavy-intensity occupational physical activity have a lower risk of CHD?OR=0.715,95% CI:0.586⁰.872 and OR=0.678,95% CI:0.533⁰.862?;people with light diet have a lower risk of CHD?OR=0.754,95% CI:0.629⁰.905?;recent encountering a major life event,family history of CHD,hypertension,hyperlipidemia,diabetes,increased risk of CHD.?2?CircRNA,miRNA and mRNA are differentially expressed between CHD case group and control group,and there is a positive/negative expression relationship between circ₀001946-miR-7-5p-PARP1/RAF1.?3?The expression levels of circ₀008507,circ₀001946 and circ₀000284 were up-regulated in peripheral blood of patients with CHD,and the expression levels of miR-153-3p,miR-7-5p and miR-379-5p were down-regulated.?4?circ₀008507,circ₀001946,circ₀000284 and miR-7-5p have a good value in diagnosing CHD,combined with the above indicators the AUC of ROC curve is 0.893?95% CI: 0.854⁰.932?,and the diagnostic accuracy is higher than a single indicator.?5?Patients with high epigenetic risk scores and non-dietary diets had a significantly higher risk of CHD.Conclusion?1?Heavy and medium-intensity occupational physical activity and light diet are the protective factors for CHD,recent encountering a major life event,family history of CHD,hypertension,hyperlipidemia,diabetes are the risk factors for CHD.?2?circ₀001946 may play an important role as a ceRNA in the development of CHD through the circ₀001946-miR-7-5p-PARP1/RAF1 regulatory axis.?3?High expression of circ₀008507,circ₀001946 and circ₀000284 is an independent risk factor for CHD,and high expression of miR-153-3p,miR-7-5p and miR-379-5p is an independent protective factor for CHD.?4?circ₀008507,circ₀001946,circ₀000284 and miR-7-5p have a good value in diagnosing CHD,the accuracy of joint diagnosis of indicators is higher than that of single indicator.?5?The epigenetic risk score and the light diet have a joint action in the prevalence of CHD.