Differentiation Of Phlegm With Coronary Heart Disease And Physical Types And The Relationship Of Apoe And Its Receptor Gene Polymorphism Of The Study

Coronary Heart Disease belongs to TCM category of "obstruction of qi in chest"," obstruction of heart qi " and "angina pectoris". After accumulating the experience for thousands years, TCM forms a full theory system in differentiation of syndromes about the cognition and treatment to CHD. The research about the syndromes is the key point. Syndromes is the description about comprehensive judgment to all information of physiological and pathological condition caused by the whole intrinsic and exogenous factor, which comprises the physiological function of the organ and all kinds of the biological, chemical, environmental, mental, climatic et al nosogenesis. The formation of syndromes is tied up with heredity, the individual constitution, the life habit and environment. Aims to explore the Phlegm syndrome (PS), Blood turbid stasis syndrome (BSS) and correlative syndromes etiology, we studied and analyzed lots of impact factors to CHD. The results are very import evidences comprehensively explaining the CHD syndromes formation and development effected by reciprocity of heredity and environment. And it offered the evidence to make the CHD syndromes diagnose standard. And it can also help us profoundly understanding the basic philosophy of TCM integrated conception of 'correspondence between man and the universe', which also can give important guidance to "prevention first" and treatment by individual.It has been an acknowledgment that the phlegm-dampness and blood-obstruction are the important nosogenesis of CHD in TCM, which is closely relatively with lipid metabolism turbulence. ApoE plays very important function in lipid metabolism. The gene locates on 19ql3.2 and shows polymorphism. It is illustrated that apoE gene polymorphism closely correlative with CHD, hyperlipemia, Alzheimer's disease and etc. The transferring lipid function of apoE is executed by combining with receptor progress. LDL-R( low-density lipoprotein receptor), one of apoE receptors, which gene is one of impact factors abouthyperllIpemia too. Owing to the tow kinds of polymorphism will affect the lipid metabolism, they should be study if we want to explore the CHD PS and BSS. And these researches will do good to intensively elucidate the molecular heredity background and etiology of CHD PS and BSS.Differentiated by Syndrome Differentiation-type standards (TCM-SDT), 200 CHD patients involved Phlegm syndrome (PS), blood stasis syndrome (BSS), Phlegm-Blood Turbid syndrome (PBTS), Non-Phlegm-Non-Blood stasis syndrome (NPNBS) were adopted in this study. Judged by'The theory of TCM constitutions", the types of constitutions of patients were six . The controls are 100 healthy cases. Blood lipids were measured by routine examine. The peripheral blood total DNA were extracted. The polymorphisms in apoE exon4, apoE intron enhancer 1 (IE1) +113 site and LDL-R exon 13 Avail site were determined firstly by using PCR to amplify the DNA sequence containing the polymorphisms site, followed by digestion with the restriction enzyme. The relativity of data was analyzed by SAS software in method of variance, co-varience, regression analysis. The impact in lipid level from association of genotype was also analyzed. And we summarized the assignment rule of different genotype, allele frequency in Phlegm and Blood stasis syndrome. In addition, the relationship between constitution and syndrome was illustrated. The susceptibility constitution to syndrome was estimated by Logistic model. In the clinic research aspect, factor analysis and cluster analysis was use to conclude the principle of four kinds of diagnose information, which could be regarded as reference to draw the diagnose standards to syndrome. In this study, it is originality that data analyses were done using the "Multivariate nonlinear network correlation analysis model with covariates", which attempted to create a new method to analyze the whole system in syndrome influenced by gene structure and functional level, circumstance, constitution type diversity. The results also give more elicitation to explore the new way studying the etiology and pathology of CHD and others complicated disease.The study demonstrated that the total cholesterol ( TC ), total triglyceride ( TG ) and low-density lipoprotein cholesterol (LDL-C) level in apoE exon4e4 allele , intron enhancer 1 +113 BspLI site G allele, or LDL-R exonl3 Avail site + allele carriers are in some degree higher than in other genotypes, especiallye4 allele carriers group. A very strong association of the apoE IE1 G allele with the ï¿¡4 allele was observed. The influence on plasma lipid levels from G was determined bye4. LDL-R exonl3 Avail site + allele also show a weaker impact thane4. The results show that the three alleles carrier are more in CHD than control.After analyzing the relationship between the Phlegm-Blood syndrome (P-B-S) and gene polymorphism, we found that three aberrance alleles 1 inked with hyper 1 ipermia condition were all combined with phlegm or phlegm correlative syndrome, which were PS, PBS or PDC. e4 carriers were distributed more in PS and NPNBS than BSS or PBS, whereas G/G genotype were more in PS and PBS than BSS or NPNBS. Three genotypes of LDL-R show no difference contribution in the four syndromes, but the + allele was more associated with PDC and BTC than other constitutions. These results supplied the creativity research on TCM P-B-S.Most of CHD were PDC, BTC and QCC. In order to analyze the constitutions and other factors' complex co-affect on syndromes, we created a new mathematics methods, multivariate logistic model to do the regression analyze about syndromes. The seeking results showed that PS was affected by PDC, QCC, whereas BSS affected by BTC, then PDC, PDC, DHC and QCC affected PBTS, NPNBS was influenced by QCC, Yin- deficiency constitution and Yang-dificiency constitution. In addition, obesity was closely correlatively with PS, BSS, PDC and BTC. If combined with noise surrounding, the PBTS would be formed. These outcome were accordant with TCM theory about "Obesity are more phlegm", "Seven emotion can cause phlegm". We found no evidence of interaction between BTC and PS, PBTS, which in some degree sustain hypothesize of "phlegm can cause blood turbid but not reverse". We take the view that phlegm and blood turbid aresame by origin, but not the same materials. Phlegm can cause blood turbid stasis but the later can't reduce the phlegm. In others words, phlegm is causation, blood turbid stasis is a consequence. Phlegm is formed in progress by accumulation of pathologic biochemistry material. The congenital constitutions do important role in the formation of phlegm syndrome. With change in structure and biochemical character, pathologic production phlegm becomes new pathogeny. There is a gradual progress from quantitative to qualitative change in phlegm turning into blood turbid stasis. Concerning with the traditional theory that blood turbid stasis can bring up phlegm, we believed it may be impossible. Only in a very limited condition, such as trauma, blood turbid can bring up edema and phlegm. In most status, blood turbid can't increase the phlegm level. Just some chemical factor reduced by blood turbid can accelerate or stimulate pathologic production phlegm become to nosogenetic phlegm. BTC can't bring to PS or PBTS. We presumed that BTC reduce the BSS affecting on thrombsystem including thrombase, fibrinokinase, platelet et al, homocystine, angiotension, vessel trauma factors and others inflammations, but it cant directly bring up turbulence of lipid metabolism.Constitution is the estate after heredity information transcription and translation. Constitution is decided by prenatal foundation. The estate of constitution can be determined by lots of factor, especially the heredity. The constitutions are affected by postnatal environment, life style and other factors. Once the estate of constitution is formed, it will be relatively stable, but not absolutely. In aspect of clinic character, the body's susceptibility to nosogenesis and the tendency of syndrome will be distinction according to the difference of constitutions. Therefore constitution determine the tendency of syndrome, which is the important factor affecting on the pathogeny, course of disease, tendency. The estate of constitution can be healthy estate and subhealthy estate, which is not distinguished between each other. After analyze the relationship betweenthe gene polymorphism and the constitutions of CHD patience, we found that three variation types of alleles which can affect lipid metabolism had closely relationship with the constitution such as PDC, BTC, QDC and DHC, which could affect P-B-S. ApoEe4 allele or correlative genotype are most closely connected with many constitutions, which almost conclude al 1 main constitutions about P-B-S. These study demonstrated that prenatal foundation or heredity background do important role in constitution type, which show certain susceptibility to some disease.CHD four sorts diagnoses information is very important to make us judge the syndrome type. This research uses the common factor, cluster and " Multivariate nonlinear network correlation analysis model with covariates " to analyze the tongue shape, the variable that solicit all pulse alike relevant symptoms and body inclusive. We found finally that the tongue is thick and greasy, slippery pulse, purple and dim tongue color is that the clinical and dialectical variable selected character of theP-B-S. The purply and dimlies tongue color is linkage with BSS. The others symptom are correlated with PS and PBS. These have offered basis on we set up the P-B-S diagnosing standard. In addition, tongue quality and tongue color and P-B-S are relevantly, the dependence of the color of tongue coating is not remarkable. This white yellow color of tongue coating is not P-B-S clinical symptom factors, which is correspondent to the experience cold syndrome and heat syndrome in TCM.Summing up the result of this study, we can see the essence that the syndrome is reciprocity, variety and open multidimensional network. It is a complicated system. So it should be proceed from whole point of view. We drew support from such technological means as cell biology, biochemistry , molecular biology , etc. , Combined with chemistry , physics, mathematics , informatics, demography and philosophy discipline relevant methods and achievements carrying on comprehensive research, the essence content of the syndrome should be announced. We should see at the same time, research about CHD phlegm syndrome from gene polymorphism...