新疆维吾尔、汉、哈萨克和回族健康人群尿液代谢轮廓分析

In metabonomic studies, various biological factors can affect the metabolic composition of biological fluids and lead to significant variability. In our previous study, it was found that there is existing difference between the urine profiles of Han and Uighur undergraduates. Most importantly, α-N-Phenylacetyl-L-Glutamine, a potential biomarkers of liver-stagnation and spleen-deficiency syndrome (LSS)-type disease, was expressed in Uighur undergraduates. The results indicated that the factor of ethic should be taken into accounts seriously in multi-ethnic co-existed region. Although Xinjiang is a high incidence area of infectious diseases, endemic diseases and noncommunicable diseases in China, the incidence of one exact disease was generally concentrated on a certain ethic group. To further study on the pathogenic mechanism of endemic diseases and increase the reliability of identified potential biomarkers, small-molecule metabolitesin urine samples collected from four main ethic of Xinjiang, Uighur, Han, Kazak and Hui, will be comprehensively investigated based on GC-MS and HPLC-MSplatform in this work. Metabolic profiling analysis will be performed, and metabolites differentially expressed will be identified among groups of different ethnic, age and sex. Furthermore, a control database would be constructed containing these metabolites differential expressed. We hope our study can increase the accuracy of pre-diagnosis and the reliability of potential biomarker of endemic disease, and provide as a scientific basis for endemic study in Xinjiang.

代谢组学研究中，性别、年龄、饮食习惯等众多因素会影响着生物样本中代谢物的组成与含量，导致相关研究结果出现显著性的变化。前期工作中我们发现维吾尔族和汉族大学生健康人群尿液代谢轮廓间存在一定差异，而且肝脾气虚症标志物在维吾尔族健康人群中表达偏高，这表明在多民族共聚地区，族别因素会对疾病代谢组学研究带来严重干扰。新疆是全国传染病、地方病及慢性非传染病高发区，发病人群表现出一定的民族性，为深入研究新疆高发病发病机理，提高相关生物标志物的可靠性，本申请拟采用GC-MS、HPLC-MS/MS等分析手段，系统研究维吾尔族、汉族、哈萨克族和回族等四个新疆主要民族健康人群尿液中小分子代谢物，进行尿液轮廓分析，寻找族别、年龄、性别等因素导致的尿液中代谢物间的差异及其分布规律，发现和鉴定差异代谢物，建立相关代谢物控制库，为新疆高发病早期诊断与疗效评价相关相关标志物的筛选提供关键物质基础。

代谢组学研究中，性别、年龄、饮食习惯等众多因素会影响着生物样本中代谢物的组成与含量，导致相关研究结果出现显著性的变化。新疆是全国传染病、地方病及慢性非传染病高发区，发病人群具有一定的民族性。前期研究工作中我们发现依赖于现有疾病相关标志物对新疆整体人群进行诊断时，会导致高假阳性率，这意味着在多民族共聚地区，族别因素可能会对疾病代谢组学研究带来严重干扰。基于上述考虑，本项目基于GC-MS和ICP-MS平台，系统研究了维吾尔和汉这两个新疆人口最多的民族健康人群尿液中小分子代谢物及微量元素的轮廓，并采用生物统计学方法考察了族别、年龄、性别等因素对尿液代谢物轮廓的影响。结果表明民族因素对代谢小分子在新疆健康人群尿液轮廓的影响贡献度最大，而性别和年龄因素相对较小。生物统计学结果表明有8个代谢小分子，D-半乳糖、苯乙酰谷氨酰胺、核糖酸内酯、半乳糖醇、肌醇、十八酸、苏氨酸、琥珀酸在两个族群尿液中的表达存在显著性差异。这些代谢物主要参与碳水化合物循环，TCA循环，脂肪酸代谢和微生物代谢。值得注意的是D-半乳糖，苯乙酰谷氨酰胺，琥珀酸为目前临床使用的疾病标志物。这说明在多民族共聚地区疾病标志物的使用应依据民族有所区别。与小分子代谢物相比，民族因素对尿液中金属元素/非金属元素分布轮廓相对较小，依赖全部样本建立的26个元素参考库可应用于维吾尔和汉族。但我们发现新疆地区居民面临砷暴露过度的风险。此外，为实现对复杂样本体系中目标化合物的高选择性和高特异性富集，发展了2种固相萃取材料合成路线，制备出3种新型固定萃取材料；为实现快速检测复杂样本中的氧化还原性组分，制备出5种新型化学修饰电极。本项目的顺利实施为深入研究新疆高发病发病机理，提高相关生物标志物的可靠性，多民族共聚地发展新的诊疗手段，设计临床实验和精准医疗提供了理论基础。