基于队列人群研究基因-环境交互作用对2型糖尿病发生风险的预测和预警

Type 2 diabetes is a life-threatening disease. Screening for the high risk individuals with type 2 diabetes is important for us to adopt the targeted strategies to prevent diabetes and decrease the morbidity and mortality of diabetes. However, the present risk predictive model of diabetes is based on the tradional risk factors and has limited predivtive ability. Therefore, it is necessary to enter the novel risk factors into the predictive model and to improve the predictive ability of the model. In the present study we will use the 1:1 matched case-control study and the prospective cohort study to collect the detailed environmental factors including lifestyle factors and to explore the gene-gene and gene-environment interactions on type 2 diabetes. In addition, the present study will calculate the genetic risk score to represent the global genetic risk factors of type 2 diabetes in an individual to examine that how the genetic risk score and their interactions with environmental factors predict the risk of type 2 diabetes. Moreover, we will further explore the potential biological mechanism of the gentic variants in the development of type 2 diabetes. Using the 1:1 matched case-control study and the prospective cohort study design at the same time, the present study will calrify the genetic factors for type 2 diabetes and their interactions with environmental factors; in addition, using the genetic risk score and their interactions with environmental factors to predict the type 2 diabetes risk will be helpful to screen the high risk subjects with type 2 diabetes and to carry out the presonal prevention and treatment for those with high risk of type 2 diabetes.

2型糖尿病严重威胁人类生命和健康。早期筛选出2型糖尿病高危人群并加强一级预防和个体化干预，将对降低糖尿病发病率和死亡率有重要作用。但基于传统危险因素构建的糖尿病风险模型预测能力有限，急需纳入新危险因素以提高模型预测能力。本项目采用病例-对照研究和前瞻性队列研究，利用标准化流行病学调查表收集主要环境因素包括生活方式资料，同时运用遗传风险评分综合评价糖尿病遗传危险因素，探讨易感基因多态性位点之间和基因-环境在糖尿病发生中的交互作用。同时探讨遗传危险评分和基因-环境因素交互作用对糖尿病发生风险的预测作用，并对糖尿病易感基因多态性位点进行功能研究。本研究结果将有助于阐明糖尿病发生中的基因-基因和基因－环境交互作用模式及其具体生物学机制；同时利用糖尿病遗传危险评分和基因-环境因素交互作用预测糖尿病发生风险，提高模型的预测能力和区分度，为糖尿病高危人群筛检和个体化干预与治疗提供科学依据。

2型糖尿病严重威胁人类生命和健康。早期筛选出2型糖尿病高危人群并加强一级预防和个体化干预，将对降低糖尿病发病率和死亡率有重要作用。但基于传统危险因素构建的糖尿病风险模型预测能力有限，急需纳入新危险因素以提高模型预测能力。本项目采用前瞻性队列研究，利用标准化流行病学调查表收集主要环境因素包括生活方式资料，同时运用遗传风险评分综合评价糖尿病遗传危险因素，探讨易感基因多态性位点之间和基因-环境在糖尿病发生中的交互作用。同时探讨遗传危险评分和基因-环境因素交互作用对糖尿病发生风险的预测作用。本研究结果发现尿铜和尿锌水平与糖尿病的风险增加，每日做饭时长可以增加糖尿病前期和高血糖的患病风险，但与2型糖尿病患病率没有关联，而儿童中期暴露于饥荒能增加成年后患2型糖尿病的风险。与低生活方式评分的人群相比，中等和高生活方式评分的人群患糖尿病的风险分别降低23%和46%；而高遗传风险人群患糖尿病的风险增加，高生活方式评分与遗传因素在2型糖尿病发生过程中没有交互作用。同时，基于上述研究结果，建立了基于中国人群的2型糖尿病风险预测模型。本项目研究结果阐明糖尿病发生中的基因－环境交互作用；同时利用糖尿病遗传危险评分和基因-环境因素交互作用预测糖尿病发生风险，提高模型的预测能力和区分度，为糖尿病高危人群筛检和个体化干预与治疗提供科学依据。