双酚A（BPA）及典型BPA替代物双酚S、双酚F是一类广泛存在的环境内分泌干扰物，实验研究发现双酚类暴露可影响糖尿病发生，但现有流行病调查缺乏可提供暴露-效应时间先后及因果关联证据的人群研究。2型糖尿病（T2DM）是一种受环境暴露及表观遗传等多因素影响的内分泌疾病，SOCS3基因DNA甲基化水平与T2DM易感性有关，且双酚类暴露会影响SOCS3蛋白水平，然而该基因甲基化修饰是否介导双酚类暴露致T2DM发病及其与暴露对T2DM的影响是否存在交互作用尚不清楚。因此本项目拟采用巣式病例对照研究，明确农村人群典型双酚类暴露与T2DM的因果关联及剂量-效应关系；结合SOCS3基因DNA甲基化检测结果，阐明双酚类暴露对SOCS3基因甲基化的影响，进一步探索暴露与表观遗传对T2DM的交互作用及SOCS3基因DNA甲基化的中介效应。研究结果将为双酚类物质的健康风险评价，T2DM病因探查及预防提供科学依据。

Bisphenol A (BPA) and BPA substitutes (bisphenol S and bisphenol F) are widespread environmental endocrine disruptors. A number of experimental studies have shown that bisphenols exposure can affect the occurrence of diabetes. Nevertheless, available epidemiology surveys such as cohort studies or prospective nested case-control studies which could provide causal evidence of the relationship between bisphenols exposure and diabetes are lacked. Type 2 diabetes mellitus (T2DM) is an endocrine disease that is influenced by epigenetic and environmental factors. The DNA methylation level of SOCS3 gene is significantly associated with T2DM, and bisphenols exposure has the ability to alter SOCS3 protein levels, suggesting the change of DNA methylation may play a role in the pathway of bisphenol exposure resulting in T2DM. However, it is unclear whether SOCS3 DNA methylation has an interaction or mediation effect on the relationship between bisphenols exposure and T2DM. Therefore, we propose to design a prospective nested case-control study in Henan rural population to determine the dose-effect relationship between bisphenols exposure and T2DM. Together with the detection of SOCS3 DNA methylation, we will further study the effects of bisphenols exposure on epigenetic modification which might be a potential mechanism, as well as the interaction between environmental exposure and epigenetics on T2DM. The results will provide meaningful information on the health risk assessment of bisphenols, and uncover the etiology, epigenetic mechanism as well as rational prevention of T2DM.