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Genetic Characteristics and the Physical Effects of CHD with Blood-stasis Syndrome

Author: WangLiPing
Tutor: YuanZhaoKai
School: Hunan University of Traditional Chinese Medicine
Course: Diagnostics of Chinese Medicine
Keywords: Coronary Heart Disease genetic epidemiology case-control study separation ratio heritability gene chip
CLC: R259
Type: PhD thesis
Year: 2011
Downloads: 141
Quote: 0
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Abstract


Objective:Discussed Genetic Characteristics of blood stasis of CHD and analyzed physical effects of blood stasis of CHDMethod:1.Document Research:This article Searched the words"coronary heart disease, blood stasis, genetic epidemiology, physical, CHD, Gene, Gene chip" to finding Document of blood stasis of CHD and summarized this Document to understand the Research that genetic characteristics of CHD and affect physical effects of blood stasis of CHD in the VIP, CNKI, Wanfang database, PubMed, Circulation, Refdoc.fr network resources2.Physical and genetic epidemiological studies:Research Methods that blood stasis of CHD is family aggregation analysis, segregation ratio, heritability, Genetic approach by Genetic epidemiological methods, case-control study3.Gene chip technology:Using Affymetrix HumanGenome U133 Plus 2.0 gene chip CHD on the family, family, non-blood stasis syndrome with coronary heart disease, family, non-blood stasis syndrome with CHD, family health, non-family CHD, non-family study healthy people, CHD Screening gene expression profiles observed. By Gene Ontology (Gene Ontology, GO) analysis of differentially expressed genes for each approved the molecular function, through the website by http://www.biocarta.com/and http://www.genome.jp/kegg/find each Where the pathway between genes and used the hypergeometric distribution of the results of statistical analysis channel, through the P value (P<0.05) determine the pathway was significant, meaningful goals screening pathway. Results:1.Document Research:CHD at this stage of the study the genetic characteristics of the study of gene peptide-based, and summarizes the potential candidate gene for CHD. Possible candidate genes with CHD (1) lipid metabolism:apolipoprotein family, ABCA family, sterol regulatory element binding protein family, LDL and oxidized, LDL receptor, HDL receptor, C5L2, lipoprotein, chymase, Scavenger receptor, CD36 receptor gene polymorphism; (2) inflammation:C reactive protein, tumor necrosis factor, interleukin, complement the family, myeloperoxidase, P substance, plasma amyloid A, Toll-like Receptor, CD40 and its receptor, selectin, integrin, leukotrienes, heat shock protein, platelet activating factor, matrix metalloproteinases, transforming growth factor, Fas ligand; (3) coagulation and fibrinolytic systems:Coagulation factors, platelet receptor, fibrinogen, plasminogen and von Willebrand, ADP receptor, collagen receptor, thromboxane synthase, cyclooxygenase, prostacyclin synthase, thromboxane receptors, prostaglandin PGI receptor (4) endothelial system:endothelin and its receptor, nitric oxide synthase and its receptor, V factor, thrombomodulin, endothelial derived growth factor, G protein, EDFIF, hepatocyte growth factor, placenta Growth factor, pregnancy associated plasma protein A; (5) renin-angiotensin aldosterone system:renin receptor, angiotensin converting enzyme, aldosterone receptor, angiotensin receptor (6) Other:A enzyme heme Kalirin VAMP, CYP family, the muscle cell-specific enhancer factor 2. The concept of physical theory, the relationship between physical fitness and syndromes, physical and genetic concerns found in the study of CHD in favor the introduction of physical theory to guide the CHD prevention, diagnosis and treatment in order to facilitate Interpretation of the genetic characteristics of blood stasis.2.Physical and genetic epidemiological studies:CHD①by case group and control group, one family, two relatives of the prevalence of CHD, the results showed significant differences (p<0.05), while patients in the family of CHD analysis confirmed that CHD does show the characteristics of familial aggregation. Conclusions of these studies suggest:CHD with a genetic tendency to blood stasis, that genetic factors in the occurrence of CHD play a role in the process; by estimating the segregation ratio and CHD Heritability obtained:Isolation of CHD ratio of 0.1296 (0.1020-0.1572), indicating that the Coronary Heart Disease is a multi-gene genetic diseases, by Falconer Estimating first and second degree relatives were 58.04% of genetic,54.80%, is moderate genetic; By Penrose’s method to estimate the genetic model, coronary heart disease and blood stasis syndrome group s/q=3.47, closer to 1/q=8.80; CHD by way of multiple genetic confirmation, the results show:when a relative degree of genetic 0.5804, the threshold model by Jiang Sanduo expected theoretical calculations, the formula for Xr=Xg-rh2ag, the results CHD incidence of disease theory of first-degree relatives was 8.00%, and the actual incidence rate of 5.89% was close to trend, indicating that relatives of CHD in the distribution in a more consistent genetic characteristics. Meanwhile relatives of CHD The heritability of disease secondary to 0.5480, its theoretical incidence rate of 6.20%, and the actual incidence rate of 4.13% was close to trend, indicating that relatives of CHD in the secondary distribution line with multi-genetic characteristics. Secondly, no-CHD gender differences in the two groups.①physical characteristics of Chinese medicine:Patients with CHD yang quality to the main body, phlegm, yin deficiency based; and physical fitness are phlegm, Yang and quality, yin deficiency based; Nine Constitutional heritability were less than 50%, the blood stasis of coronary heart disease in the family’s physical environment is greater than genetic influences. In other words, physical impact of Coronary Heart Disease as a relevant factor, but for Coronary Heart Disease does not play a decisive role of genetic. This is consistent with the clinical, Coronary Heart Disease in clinical development and bad habits and diet are closely related.③In the case of groups the correlation of physical stasis that the incidence of CHD with the main body there was a correlation (p<0.05). Heritability of CHD study, results suggest that:the genetic constitution of nine were less than 50% of the degree, so in Coronary Heart Disease in the family’s physical environment is greater than genetic influences. Physical impact of CHD as a relevant factor, but for CHD does not play a decisive role of genetic. This is consistent with the clinical, CHD in clinical development and bad habits and diet are closely related.3.Gene chip technology:The results showed that differences in gene CHD based mainly on inflammatory factors. When p<0.05 when the study found differences in CHD gene expression mainly related to the following types of gene expression changes in the Department:①Chemokine;②Cytokine interleukin;③Department of matrix metalloproteinases MMPs;④Fibroblast growth factor;⑤cytochrome oxidase P450 (CYP) system;⑥hypoxia-related Genes. The BioCarta and KEGG pathway analysis of CHD-related differences in the genetic gene, to further verify the Coronary Heart Disease mainly related to inflammation and plaque formation, endothelial damage aspects. Department of CHD at home, it found in Phlegm with water and adjusting the AQP4 regulation in gene expression.Conclusion:1. Which emphasis on "Distinguishing physical", "syndrome"and many other integrated use of diagnostic analysis is use for CHD comprehensive understanding of the nature2. CHD with a genetic tendency to blood stasis, that genetic factors in the occurrence of CHD play a role in the process. Coronary Heart Disease is a multi-gene genetic diseases, the relationship is moderate genetic heritability.3. CHD is the main body Main yang quality, phlegm, yin deficiency-based, and physical fitness is phlegm, Yang nature, yin deficiency based. CHD Constitution and there was a correlation.4. CHD mainly related to differences in gene expression①Chemokine;②Cytokine interleukin;③Department of matrix metalloproteinases MMPs;④Fibroblast growth factor;⑤cytochrome oxidase P450 (CYP) system;⑥hypoxia-related Genes.5. The BioCarta and KEGG pathway analysis of CHD-related differences in the genetic gene, to further verify the CHD mainly related to inflammation and plaque formation, endothelial damage aspects.

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