| Hyperlipidemia is a dangerous element of many diseases that show high incidence and high death rate, such as heart and brain vascular diseases, diabetes, tumour, hypertension and nephropathy, and is related with many common diseases, frequent diseases, difficult and complicated diseases in many systems of the total body. In Chinese Medical Science, hyperlipidemia is thought to be phlegm syndrome, and is homologous with the blood stasis according to the theory of Chinese Medical Science. Analyzed form clinical behavior, hyperlipidemia belong to the " phlegm" and " blood stasis" category. At present, "phlegm-stasis syndrome" is a major pathogeny and mechanism of hyperlipidemia, and the major clinical treatment to it is dispelling phlegm and removing blood stasis according to ZangFu function.Apolipoprotein is protein component of the plasma lipoprotein, and is core part to determine the struction, function and metabolizability of lipoprotein. Apolipoprotein gene polymorphism is a major inherited factor that effect blood lipid metabolizability. ApoA5-1131T/C polymorphism and ApoC3-482C/T polymorphism is related with variety of triglyceride concentration in plasma. ApoE is the high-affinity ligand of low-density lipoprotein acceptor, and ApoE extron 4 polymorphism is related with variety of cholesterol concentration in plasma. More researches show that phlegm and blood stasis is related with dyslipidemia, and show that the increasing blood lipid concentration is the major biochemical substance base of the phlegm in blood. The relation between syndrome and gene polymorphism is till the major method to study syndrome specificity and its happening, its development, and the method to find new treatment targets. It is great significance in both theory and practice to find out the relation.Objectives Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, this paper makes researches on the relation between the gene polymorphism (including apoA5, apoC3 and apoE gene polymorphism) and hyperlipidemia phlegm and blood stasis syndrome, and the effect of gene polymorphism on the clinical treatments to the hyperlipidemia phlegm and blood stasis syndrome. This paper offers the clinic medicine therapy the theoretical and experimental evidence for deepening individualization treatment.Method Using PCR-RFLP methods, we analyzed the genotypes of ApoA5-1131T/C, ApoC3-482C/T and apoE extron 4 in 172 patients with hyperlipidemia phlegm and blood stasis syndrome and 80 healthy subjects, and their serum levels of lipids are also estimated by biochemical methods.According to the double-blind, double-dummy randomized parallel clinical principle, the treatment continues for four weeks. One hundred and seventy-two cases of hyperlipidemia phlegm and blood stasis syndrome are divided into observation group (n=87) and control group (n=85) . The observation group is treated by TiaoZhiTongMai granule. The control group was treated by XueZhiKang capsule. Clinical symptom and serum concentration of lipid are observed before and after the treatment.Result1 Effect of different apolipoprotein gene polymorphism on metabolizability of blood lipid in hyperlipidemia phlegm and blood stasis syndromeThe C allele frequency of the apoA5-1131T/C in the group of hyperlipidemia is remarkably higher than that in the health control group(0．38 to 0．29) , but apoC3 and apoE extron 4 locus has no statistically significant difference between the two groups.The CC genotype of apoA5-1131T/C is related with the increase of TG concentration, and with the decrease of HDL-C concentration, but there shows no statistically significant difference among the lipids concentration of different genotypes.At the apoC3-482C/T locus, the concentration of TG is highest in three genotypes of TG, CT and CC, but there is no statistically difference.E3/4 genotype of apoE extron 4 relates with the increase of LDL-C concentration and apoB concentration, but there is no statistically significant difference between the other lipids concentration.2 Relativity between main clinic symptom of hyperlipidemia phlegm and blood stasis syndrome with different apolipoprotein gene polymorphismAt the apoA5-1131T/C locus, the patient with C allele has positive correlation with chest disease symptom compared with the patient without C allele. The patient with CC genotype has positive correlation with chest disease symptom compared with the patient with TT genotype.At the apoC3-482C/T locus, the patient with C allele has positive correlation with heart-throb symptom compared with the patient without C allele.To theε4 allele at apoE extron 4 locus, the patient with E3/4 genotype has negative correlation with petechia of tongue symptom compared with E3/3, and the patient with E3/3 genotype has positive correlation with heart-throb symptom compared with E2/3 genotype, and the patient with E3/3 genotype has positive correlation with insomnia symptom compared with E3/4 genotype.At the apoA5-1131T/C locus, among the patients with the habit of smoking or drinking, the CC genotype has positive correlation with top-heavy like wrap and TT genotype has positive correlation with poor appetite symptom.Among the patients with the habit of excessive consumption of fatty and sweet foods, at the apoC3-482C/T locus, TT genotype has positive correlation with heart-throb symptom.Among the patients with the habit of smoking or drinking, at the apoE extron 4 locus, E3/4 genotype has positive correlation with obesity symptom.3 Effect of different apolipoprotein gene polymorphism and living habit on the clinic curative effect of correspond medicine in Hyperlipidemia Phlegm and Blood Stasis Syndrome.1) Effect of correspond medicine on the curative effect and total syndrome scoresAs the correspond medicine to cure hyperlipidemia phlegm and blood stasis syndrome, TiaoZhiTongMai granule has the same curative effect in adjusting serum concentration of lipid with the XueZhiKang capsule(79．31 % to 80．00% in total efficient of curative effect), but has obvious curative effect in syndrome(total scores) than the XueZhiKang capsule.2) Effect on curative effect in adjusting serum concentration of lipid using correspond medicineWhen using correspond medicine, at the apoA5-1131T/C locus, it is found that it decreases obviously in the concentration of TC, TG, LDL-C, apoB and increases obviously in the HDL-C concentration among the patients with TT genotype, and that it decreases obviously only in the concentration of TC, LDL-C among the patients with CT genotype, and that it decreases obviously only in the concentration of TC and TG among the patients with CC genotype. To the ratio of TG concentration before to after treatment using correspond medicine, its value with the CC genotype is biggest than that with the CT and TT genotype. To the ratio of HDL-C concentration before to after treatment using correspond medicine, its value with the TT genotype is biggest than that with the CT or CC genotype.When using correspond medicine, at the apoC3-482T/C locus, it is found that it decreases obviously in the concentration of TC, TG, LDL-C, apoB among the patients with CC genotype, and that it decreases obviously only in the concentration of TC, LDL-C, apoB among the patients with CT genotype, and that it decreases obviously only in the TG concentration among the patients with TT genotype. But there shows no statistically significant difference among the ratio of blood lipid concentration before to after treatment for different genotypes.When using correspond medicine, at apoE extron 4 locus, it is found that it decreases obviously in the concentration of TC, TG, LDL-C, apoB and not decreases obviously in the HDL-C among the patients with E3/3 or E3/4 genotype, and that it increases obviously only in the concentration of HDL-C among the patient with E2/3 genotype. The ratio of LDL-C before to after treatment increases gradually with the sequence of E2/3, E/3/3 and E3/4, and the ratio among the patients with E3/4 genotype is biggest than that with other two genotypes.When using correspond medicine, the ratio of LDL-C before to after treatment among the patients with the habit of smoking is smaller obviously than the ratio among the ones without smoking. Similarity, the ratio for the patients with the habit of drinking is smaller than that without drinking, but the ratio for the patients with the habit of excessive consumption of fatty and sweet foods is bigger obviously than that without the habit.3) Effect on the relation between correspond medicine with clinic curative effectThere shows statistically significant difference between the curative effect in adjusting clinic symptom with the gene polymorphism at apoA5-1131T/C locus or at the apoC3-482T/C locus At the apoE extron 4 locus, the curative effect of top-heavy like wrap and chest diseases symptom among the patients with E3/4 genotype is worse than that with E3/3 genotype. curative effect of heart-throb symptom withε2 allele is better than that withoutε2 allele, and the curative effect with E2/3 genotype better than that with other genotypes. The curative effect of insomnia symptom withε4 allele better than that withoutε4 allele, and the curative effect with E3/4 genotype is better than that with E3/3 genotype. The curative effect of insomnia symptom become better with the sequence of E2/3,E3/3,E3/4 genotype.Among the patients with the habit of smoking when using the correspond medicine, at apoC3-482T/C locus, the curative effect of top-heavy like wrap symptom for the ones with CC genotype is worse than that with TT genotype, and the curative effect becomes worse gradually with the sequence of CC,CT,TT genotype. At apoE extron 4 locus, the curative effect of top-heavy like wrap symptom for the ones with E3/4 genotype is better than that with E3/3 genotype.Among the patients with the habit of drinking when using the correspond medicine, at apoC3-482T/C locus, the curative effect of chest disease and little food symptom for the ones with C allele is worse than that without C allele. At apoE extron 4 locus, the curative effect of top-heavy like wrap symptom for the ones with E3/4 genotype is worse than that with E3/3 genotype.Among the patients with the habit of excessive consumption of fatty and sweet foods when using the correspond medicine, at apoA5-1131T/C locus, the curative effect of petechia of tongue symptom for the ones with TT genotypeis worse than that with CT genotype, and the curative effect becomes worse gradually with the sequence of CC,CT,TT genotype. At apoC3-482T/C locus, the curative effect of a little food and the slipping pulse symptom for the ones with CC genotype is worse than that with the TT or CT genotype.Among the patients without the habit of smoking when using the correspond medicine, atapoE extron 4 locus, the curative effect of heart-throb symptom for the ones with e 2 allele isbetter that withoutε2 allele. And the curative effect of insomnia symptom for the ones withε4 allele is better than that withoutε4 allele and the curative effect with E3/4 genotype isbetter than with E3/3 genotype, and the effect becomes better gradually with the sequence of E2/3, E3/3, E3/4 genotype.Among the patients without the habit of drinking when using the correspond medicine, at apoE extron 4 locus, the curative effect of heart-throb symptom for the ones withε2 allele is better than that withoutε2 allele, and the curative effect with E2/3 genotype is better than that with E3/4 genotype, and the effect becomes better gradually with the sequence of E3/4, E3/3 , E2/3 genotype.Among the patients without the habit of excessive consumption of fatty and sweet foods when using the correspond medicine, at apoE extron 4 locus, the curative effect of insomnia symptom for the ones withε4 allele is better than that withoutε4 allele, and the curative effect with E3/4 genotype is better than that with E3/3 genotype, and the effect becomes better gradually with the sequence of E2/3, E3/3, E3/4 genotype.Conclusion1 At apoA5-1131T/C locus, CC gene type is probably one of the impressionable genes to increase TG concentration and decrease HDL-C concentration in hyperlipidemia phlegm and blood stasis syndrome. At apoE extron 4 locus, E3/4 genotype is one of the impressionable genes to increase LDL-C concentration in hyperlipidemia phlegm and blood stasis syndrome. The fact imply: the CC genotype at apoA5-1131T/C locus, and the E3/4 genotype at apoE extron 4 locus is related with phlegm and blood stasis syndrome. ApoC3-482C/T gene polymorphism is not related with metabolization of lipid in plasma in hyperlipidemia phlegm and blood stasis syndrome.2 ApoA5-1131T/C, apoC3-482C/T or apoE extron 4 gene polymorphism is probably concerned with the happening of hyperlipidemia phlegm and blood stasis syndrome. The habit of smoking, drinking or excessive consumption of fatty and sweet foods is probably concerned with the happening of hyperlipidemia phlegm and blood stasis syndrome.3 ApoA5-1131T/C, apoC3-482C/T or apoE extron 4 gene polymorphism has influence on curative effect in adjusting serum concentration of lipids using correspond medicine in hyperlipidemia phlegm and blood stasis syndrome, and is probably genetic factors of the difference curative effect of the individuals in adjusting serum concentration. The habit of smoking, drinking or excessive consumption of fatty and sweet foods has influence on curative effect in adjusting serum concentration of lipids using correspond medicine in hyperlipidemia phlegm and blood stasis syndrome, and is probably exogenous factors of the difference curative effect of adjusting serum concentration. The difference of curative effect of the individuals in adjusting clinic symptom using correspond medicine in hyperlipidemia phlegm and blood stasis syndrome is determined by the genetic and exogenous factors.Gene polymorphisms has influence on metabolization of lipide and lipoprotein in plasma, clinic symptom in syndrome and curative effect using correspond medicine in hyperlipidemia phlegm and blood stasis syndrome, and is genetic factor of individual difference. The bad habit has obviously influence on effect when using correspond medicine in hyperlipidemia phlegm and blood stasis syndrome, and is exogenous factor of individualization difference. So, not only "using the same curative method in difference disease" and "using difference curative method in the same disease" are applied to cure the disease, but "using difference curative method in the same syndrome" can enhance the whole curative effect according to the genetic and exogenous factors. It is great significance to offer clinic medicine therapy a theoretical and practical evidence for deepening individual treatment, and to show the scientific and theoretical characteristic by the diagnosis and treatment principle of "because of difference time, because of difference place, because of difference person" in Chinese Medical Science.
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