利用生物信息学手段对糖尿病和前驱糖尿病进行判别分析的相关研究

发布时间：2018-07-15 18:27

【摘要】：目的 II型糖尿病(T2D)是一种世界性的疾病。据估计，全世界有3.47亿人患有糖尿病。因此本研究探讨用全血白细胞分子谱系的方法来鉴别、正常人和前驱糖尿病患者的可行性，试图找出差异性基因来更深层次的研究糖尿病的发病机制。方法总共收集了167个血液样本，其中包括T2D患者87人，正常人56人，前驱糖尿病患者24人。T2D诊断标准为体重指数（Body mass index, BMI）明显增高以及空腹血糖含量大于126mg/dl，或口服葡萄糖耐量实验中2h血糖含量大于200mg/dl。用含约20,000个基因的安捷伦Oligo芯片对所有样本进行基因表达谱分析。用Gene Spring10.0软件对基因芯片数据进行分析，找到倍数变化值大于2，，p值小于0.05的基因，并利用DAVID在线分析工具对差异基因进行染色体定位和功能分析。用spss16.0整合样本的所有参数构建判别模型，最后用判别模型对样本进行分类。结果倍数变化值大于2的基因有79个，差异基因染色体定位分析发现1个差异基因未知其定位，其余78个差异基因在1号染色体上分布最多，有9个，其次有7个差异基因在2染色体上。从差异基因功能分类看，调控细胞增殖的差异基因最多。79个差异基因结合年龄、性别、种族共82个参数，得出最优判别模型，该模型可以确认95.1%的样本，其中T2D组正确率95.9%，正常对照组正确率91.5%，前驱糖尿病组正确率100%。结论差异基因散在分布于各染色体，以1、2号染色体最多。调控细胞增殖的差异基因在T2D发生过程中发挥重要作用。本实验用79个基因结合年龄、性别、种族构建的模型是可以较好的区分T2D、正常人和前驱糖尿病患者，这将为糖尿病的机制相关研究或治疗提供新的理论依据。
[Abstract]:Objective Type 2 diabetes mellitus (T 2 D) is a worldwide disease. An estimated 347 million people worldwide suffer from diabetes. Therefore, this study explored the feasibility of identifying normal and prediabetic patients by whole blood leukocyte molecular lineage, and trying to find out different genes to further study the pathogenesis of diabetes. Methods A total of 167 blood samples were collected, including 87 T2D patients and 56 normal subjects. The diagnostic criteria of .T2D in 24 patients with prediabetes mellitus were body mass index (BMI) and fasting blood glucose content (FBG) > 126mg / dl, or 2 h glucose level > 200mg / dlin oral glucose tolerance test (OGTT). All samples were analyzed with Oligo microarray containing about 20 000 genes. The gene chip data were analyzed by Gene Spring 10.0 software, and the genes whose multiple change value was more than 2p < 0.05 were found. The differential gene chromosome location and function analysis were carried out by DAVID online analysis tool. The discriminant model is constructed by integrating all the parameters of the sample with spss16.0. Finally, the discriminant model is used to classify the sample. Results there were 79 genes whose multiple variation value was greater than 2. One differential gene was found to be unknown by chromosome mapping analysis. The remaining 78 genes were most distributed on chromosome 1, and 9 genes were located on chromosome 1. The next seven differentially expressed genes were on chromosome 2. According to the functional classification of differentially expressed genes, the number of differentially expressed genes in cell proliferation was the highest. There were 82 parameters including age, sex and race. The optimal discriminant model was obtained, which could confirm 95.1% of the samples. The correct rate of T2D group was 95.9%, that of normal control group was 91.5%, and that of prediabetes group was 100%. Conclusion the differential genes were scattered in all chromosomes, most of which were on chromosome 1 and 2. Differential genes that regulate cell proliferation play an important role in the development of T2D. In this study, 79 gene-binding age, sex and race models can be used to distinguish T _ 2D, normal and prediabetic patients, which will provide a new theoretical basis for the study or treatment of diabetes mellitus mechanism.
【学位授予单位】：武汉科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

【共引文献】