NAD+/SIRT1代谢通路介导的抗炎反应及烟酰胺超载与2型糖尿病的关系研究

项目名称： NAD+/SIRT1代谢通路介导的抗炎反应及烟酰胺超载与2型糖尿病的关系研究

项目编号： No.81460159

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张海英

作者单位： 广西医科大学

项目金额： 48万元

中文摘要： 2 型糖尿病（T2DM）是遗传因素与环境因素长期交互作用的结果，且有研究表明可能是一种低度炎症性疾病。我们的前期研究发现细胞粘着分子通路（CAMs）可能参与T2DM的炎症机制。在此基础上，我们采用生物信息学技术筛选出了能抑制CAMs通路功能的NAD+/SIRT1代谢通路。同时有文献报道烟酰胺超载与T2DM相关。因此，我们拟开展以人群为基础的病例对照研究，分析烟酰胺超载等环境危险因素、NAD+/SIRT1代谢通路中的SIRT1、ENPP1、NAMPT、NNMT、AOX1等候选基因的多态性及其表达与T2DM的关联。并进一步分析CAMs和NAD+/SIRT1两条通路上基因-基因、基因-环境的交互作用，构建多因素T2DM风险预测模型。本研究的开展，将进一步从遗传与环境及其相互作用的角度探索T2DM中的炎症机制，并最终为T2DM的高危人群筛选、预测预警和综合防治提供依据。

中文关键词： 2型糖尿病；烟酰胺腺嘌呤二核苷酸；去乙酰化酶1；通路分析；关联研究

英文摘要： Type 2 diabetes mellitus (T2DM) is a complex disease influenced by both environmental and genetic factors. Recent researches have shown that low-grade chronic inflammation might contribute to the development of T2DM. Our previous study have found that cell adhesion molecule pathway (CAMs) may be associated with the inflammation process in T2DM. Based on this, we use bioinformatic technologies to screen out NAD+/SIRT1 metabolic pathway which can suppress CAMs pathway's function. The connection of nicotinamide overload to T2DM is reported by other researches as well. Therefore, we attempt to conduct a population-based case-control study to investigate the effects of environmental risk factors (such as nicotinamide overload), polymorphisms and expressions of candidate genes (SIRT1, ENPP1, NAMPT, NNMT, AOX1) on NAD+/SIRT1 metabolic pathways on T2DM. Advanced analysis of gene-gene interaction, gene-environment interaction based on these two pathways will be performed as well. All of these will lead to the construction of a multi-factors risk prediction model of T2DM. The accomplishment of this research, will be helpful in the exploration of inflammation pathogenesis in T2DM from the perspective of the interaction between genetic and environmental effects. And it will provide a reference for screening high-risk population and be useful in prediction, comprehensive prevention, and control of T2DM as well.

英文关键词： Type 2 Diabetes Mellitus;nicotinamide adenine dinucleotide(NAD+);Sirtuin 1(Sirt 1);pathway analysis;association study