在冠心病发生发展过程中，外界因素影响基因表达的机理和途径至今尚无明确结论。本课题研究目标：(1) 探讨全基因组及候选基因DNA甲基化水平与冠心病之间的联系以及环境—DNA甲基化—遗传的联合作用；(2) 阐明DNA甲基化水平的长期变化趋势及其影响因素，探讨心血管病代谢性危险因素与DNA甲基化水平之间的时间序列关系及其对冠心病易感性的影响。本研究拟采用巢式病例—对照研究，在中国慢性病前瞻性研究队列人群中选择2014—2017年间新发冠心病患者250例及匹配对照250例，收集发病前基线和随访调查（间隔10年）的问卷、体检、生化和DNA甲基化信息。DNA甲基化的测定采用Illumina公司的DNA甲基化450芯片。统计分析采用条件Logistic 回归、交互作用分析、多元线性回归和交叉时间序列分析 。本研究旨在从分子水平上揭示环境—遗传交互作用的机理，为冠心病的干预措施提供科学依据。

The mechanisms and pathways of how non-genetic factors influence gene expression during the development of coronary heart disease (CHD) are largely unknown. The specific aims of the proposed research include (1) to explore association of CHD with genome-wide and gene-specific DNA methylation and the joint effect of environment-DNA methylation-gene, (2) to demonstrate longitudinal changes of DNA methylation and its influencing factors, and examine the temporal relationship between cardiovascular metabolic risk factors and DNA methylation as well as its impact on the liability of CHD. The proposed research will use a nested case-control study design. New incident CHD cases (n=250) occurred during 2014 – 2017 will be selected from the China Kadoorie Biobank (CKB) cohort along with 250 eligible controls. Two repeated measured information on questionnaire survey, physical examination, blood glucose, insulin and lipid, as well as DNA methylation levels will be collected at baseline and follow-up with an average interval of 10 years. DNA methylation levels (at 480,000 CpG sites of the whole genome) of baseline and follow-up DNA samples (10 years apart) will be determined using Illumina HumanMethylation450 BeadChip; statistical methods of conditional logistic regression, interaction analysis models, multiple linear regression and cross-lagged analysis models will be applied. The findings of the proposed research will reveal the mechanisms of the environment-gene interaction at a molecular level, and thus, provide evidence for the intervention and personal treatment strategies for the prevention of CHD.