Study On Relationship Between The Serum Levels And Gene Polymorphisms Of Interleukin-6,Intercellul Aradhesion Molecule-1,Apolipoprotein E And The Phelgm And Blood Stasis Syndrome In Patients With Coronary Heart Disease

Background and ObjectiveThe causes of coronary heart disease (CHD) have been intensely scrutinized for the last few decades. Since the classic risk factors only explain half of the causes of the patients with CHD, additional risk factors based on molecular genetics are now being sought. The main defining pathologic feature of CHD is atherosclerosis. Biochemical and cellular interaction that define the atherosclerotic process are believed to reflect bodily responses to injury or assault on vascular endothelium. Several studies have described that in both the coronary astherosclerotic plaque and the shoulders of the lesion inflammatory immune cells such as macrophages and T cells enter, accumulate, and are activated and apoptosis may occur. The recent experimental and clinical evidence showed that a key component in the development and progression of atherosclerosis involves recruitment and binding of circulating leukocytes (primarily monocytes) to the vascular endothelium mediated by a diverse array of inflammatory cytokines. The earliest changes that precede the formation of lesions of atherosclerosis take place in the endothelium. These changes include leukocyte recruitment and expression of pro-inflammatory cytokines (TNF, IL-I, IL-6) characterize early atherosclerosis, and then, macrophages after activation in intima uptake oxidized low-density lipoprotein (ox-LDL) and secrete pro-inflammatory cytokines such TNF, IL-1 and chemoattractants which further activate mononuclear cells, induce cell proliferation, and help define and localize the inflammatory response at the sites of lesions. might contribute to the predisposition to atherosclerosis, exacerbate granuloma formation, or modulate disease severity. Gene polymorphisms that influence the capacity for producing inflammatory mediators or the capacity of monocytes and lymphocytes to respond to inflammatory stimuli may increase the risk of atherosclerosis and CHD. It is important to research the relationship between gene variants of inflammatory molecules and CHD.In this study, we just focuses on the association between ICAM-1, IL-6 as well as ApoE and CHD. The distribution of genotypes and alleles in CHD group and in controls were compared to examine the association between gene polymorphism and CHD, taking the plasma levels of cytokines and lipid into account. The aim to the present study was, therefore, to provide some evidence for finding susceptibility genefor CHD and to explore the mechanism of CHD further.Methods: 97 patients with CHD were divided into three groups according to syndrome differentiation, including syndrome of phlegm(PS), syndrome of blood stasis(BSS) and syndrome of phlegm-blood stasis blocking(PBBS); 35 healthy volunteers were included in control group. Blood lipids ofICAM-1,IL-1 and ApoE were measured by ELASI, Total DNA of peripheral blood was extrasted. ICAM-1,IL-1 and ApoE genotypes were determined by polymerise chain reactior; restriction fragment length polymorphism (PCR-RFLP) technique. All data were analyzed by SPSS software.)Results and conclusion:1 The levels of soluble IL-6,ICAM-1 and ApoE were elevated in coronary heart disease groups as compared with the control group (P＜0.01) . It meaned that the three were related to complications of coronary heart disease. The levels of soluble IL-6,ICAM-1 and ApoE can be used as a marker of the presence of coronary heart disease.2 The levels of soluble IL-6 was elevated in syndrome of phlegm-blood stasis blocking group and syndrome of blood stasis group as compared with syndrome of phlegm group (P＜0.05). The levels of soluble ICAM-1 was elevated in syndrome of phlegm-blood stasis blocking group and syndrome of phlegm group as compared with syndrome of blood stasis group (P＜0.05). The levels of soluble ApoE was elevated in syndrome of phlegm-blood stasis blocking group and syndrome of blood stasis group as compared with syndrome ofphlegrn group (P＜0.05) .3 The distributions of IL-6 gene 174G/C polymorphism were not different between coronary heart disease group and control group (P＞0.05), These results suggest that the inerleukin 6 gene-174G/C polymorphism was not associated with coronary heart disease. The frequencies of the E allele were significantly higher in coronary heart disease group than that of controls (P＜0.05). The relative risk suffered from coronary heart disease of E allele was 4.65 times of the K allele (OR＝4.65, 95%CI: 1.052～3.151). it suggested that the ICAM-1 gene K469E polymorphism was not associated with coronary heart disease. The occurrence rate ofε4 allele of ApoE in patients with CHD was 17%, significantly higher than 7% in the control group (P＜0.01), and the E3/4 genotype was especially more frequent (P＜0.05) (OR＝4.65, 95%CI: 0.996～7.126).It meaned thatε4 allele was associated with coronary heart disease.4 The distributions of IL-6 gene 174G/C polymorphism and the ICAM-1 gene K469E polymorphism were not different between coronary heart disease group and control group (P＞0.05). The frequencies ofε4 allele and E3/4 genotype in patients with syndrome of phlegm group were significantly higher than those in patients with phlegm-blood stasis blocking group and syndrome of blood stasis group (P＜0.05). It said that ApoEε4 allele, especially E3/4 genotype, was the risk factor of coronary heart disease. There was a relatively close relationship between patients with ApoEε4 allele and syndrome of phlegm. It maid be one of the main susceptible genes in coronary heart disease patients withsyndrome of phlegm.5 Logistic regression analysis showed that there were correlation between coronary heart disease and smoking, diabetes, LDL-C,TG,IL-6 and ICAM-1 but IL-6 gene 174G/C polymorphism and ICAM-1 gene K469E polymorphism.