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Based On The Yin Deficiency And Yang Deficiency Constitution Health Microscopic Identification Study Of Gene Expression

Posted on:2014-01-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:R X YuFull Text:PDF
GTID:1224330398952825Subject:Basic Theory of TCM
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Background and Objective:Constitution identification method, which deeply reflects the stable state of the human body, is an effective way to manage health problems with Chinese characteristics. Genomics research based on constitution identification is a way to obtain the microcosmic information of health. By using genome-wide expression analysis of molecular biology of constitution characteristics we can preliminary grasp the microscopic features of biological information concerning with health.We have tried to select two typical constitution samples--yang-deficiency constitution and yin-deficiency constitution for analysis, to reveal their biological characteristics, and help microscopic identification research on health conditions, and provide the basis in identification of different constitutions, Based on the research on the microscopic biological health information,our aim is to provide the molecular basis for management of pat ient s with the yin-deficiency constitution and yang-deficiency constitution, and prevent relevant diseases. After that we may be able to do something for the health management system.Methods:According to the criterion of the yang-deficiency,yin-deficiency and normal constitutions, which were confirmed by the four examinat ions used by TCM doctor,12patients with the yin-deficiency constitution,12patients with of the yang-deficiency constitution and8patients with the normal constitution were enrolled in the study. Their peripheral blood sampling was collected, of the peripheral blood mononuclear cells were separated within2hours,and total RNA in white blood cells were extracted. Using an Affymetrix3’IVT expression profile chip, total DNA was synthesize and labeled.Chip synthesis and fluorescence labeling, and scanning were done. The peripheral blood of the gene expression spectrum of the subjects with yin-deficiency,yYang-deficiency and normal constitutionswas obtained. To investigate the relationship between the constitution and classification of gene by gene clustering and classifier study, and explore the application of the genetic classifier in constitution identification. At the same time, the biological function of varied expressiongenes and pathways of yin-deficiency and yang-deficiency constitution were evaluated. The purpose was to explore its molecular biological basis in healthy condition.Results:1. All the genes of32samples can be gathered into three categories, and this was very conform to the real Chinese medicine constitution classification.2. Through genetic classifier which can distinguish three types of constitution on228probe, and the four parameters of sensitivity, specificity, positive predictive value,negative predictive were significant.3. When the q-value (%)<5%and the Fold Change>2or<1/2, there is232differentially expressed genes,223were up-regulated and9down-regulated. Different genes gathed to35significant different pathways:mainly related to autoimmune disease related pathways, sugar metabolic pathways, lipid metabolic pathways, cancers pathways. Compared with normal constitution group, Yang-deficiency constitution and the yin-deficiency constitution group both have common60different expressed genes, in which there are three opposite expressed genes, nameed FFAR2, GPR109B, NAMPT. Comparison ofyin-deficiencyconstitution, Yang-deficiency constitution is raised, FFAR2(221345_at) Fold Change≈6.7796, GPR109B (205220_at) Fold Change≈7.6858, NAMPT (217739-s_at) Fold Change=6.1773(P<0.05)4. When the q-value (%)<5%and the Fold Change>2or<1/2, there is155differentially expressed genes between yin-deficiency constitution group and normal constitution group in gene expression feature maps,92were up-regulated and63down-regulated; there is203differentially expressed genes in gene expression feature maps between yang-deficiency constitution group and normal constitution group,with51were up-regulated and152down-regulated. differentially expressed genes of yin-deficiency constitution mainly involved in the biological processes are:immune response, inflammatory response, apoptosis, DNA methylation, regulation of insulin secretion, calcium-mediated signaling, glucose metabolism, regulation of lipid catabolism, response to ATP, etc. Different genes gathed to44significant different pathways, Tcell receptor signaling pathway, Toll-like receptor signaling pathway, B cell receptor signaling pathway, Jak-STAT signal ing pathway, MAPK signal ing pathway, Systemic lupus erythematosus, Autoimmune thyroid disease, Type Ⅱ diabetes mellitus, Alzheimer’s disease and many cancer parthways. Differentially expressed genes Yang-deficiency constitution of mainly involved in the biological processes are:immune response, inflammatory response, signal transduction, carbohydrate metabolism, regulation of insulin secretion, glycerol metabolism, fat cell differentiation, starch catabolism, response to ATP, oxidation reduction, etc.Different genes gathed to35significant different pathways:MAPK signaling pathway, Antigen processing and presentation, Toll-like receptor signaling pathway, T cell receptor signaling pathway, Wnt signal ing pathway、Peptidoglycan biosynthesis, B cell receptor signaling pathway, Systemic lupus erythematosus, Asthma, Autoimmune thyroid disease, Epithelial cell signaling in Helicobacter pylori infection,Alzheimer’s disease,Type I diabetes mellitus, BIadder cancer, and Colorectal cancer.Conclus ions:1.Yin-deficiency constitution, yang-deficiency constitution and normal constitution all have their feature gene expression spectrum.2. Chinese medicine constitution classification is very conform to the genetic classifier result. Through preliminary genetic classifier can distinguish yin-deficiency constitution, yang-deficiency constitution and normal constitution, and it provides methodology basis for health state of microscopic identification research.3. Yin-deficiency and yang-deficiency constitution were significantly different on the gene expression. Mainly reflects that there was a big difference between the Yang-deficiency constitution and yin-deficiencyconstitution in immune function, energy metabolism, lipid metabolism, glucose metabolism, nervous system, and in tumor cancer disease, etc. Found some glucolipid metabolism related genes, expression of Yang-deficiency constitution andyin-deficiency constitution were contrary or is greatly different, Yang-deficiency constitution is far higher than that of yin-deficiency constitution. Research results show that the Yang-deficiency constitution and yin-deficiency constitution constitution was reverse differences on glucolipid metabolism, which conform to the opposite metabolism of body heat characteristics of the yang-deficiency constitution and yin-deficiency constitution. This may be an evidence that Yang-deficiency constitution feel cold and yin-deficiency constitution feel hot.But both kinds of constitution has an immune deficiency, have immune deficiency disease and tumor cancer. But its mechanism is complicated, related mechanism needs further research.4. By studying the characteristics and differences between yin-deficiency constitution and yang-deficiency constitution in peripheral blood gene expression, This is the combination of macro and micro modern interpretation to the constitution identification method, and it provides a molecular biological basis for forming TCM health status recognition system which based on the constitution identification.
Keywords/Search Tags:Yin-deficiencyconstitution, Yang-deficiency constitution, Geneexpression spectrum, The constitution identification method, Geneticclassifier, Health status
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