| Background and Objective: Coronary heart disease (CHD) is a complex disease and thought to be the product of genetic susceptibility and an unknown antigenic stimulus from the environment. 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-1, 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.Recently, there is growing evidence for the contribution of genetic polymorphisms to interindividual difference in the regulatory mechanisms of inflammatory cytokine production. Therefore, particular variant cytokine genotypes might contribute to the predisposition to atherosclerosis, exacerbate granuloma formation, or modulate disease severity. Because the inflammatory response in AS is characterized by the production of increased amounts of several pro-inflammatory cytokines at sites of disease, including TNF, IL-1 and E-selectin. In this study, we just focuses on the association between TNF family, IL-1 family as well as E-selectin 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 gene for CHD and to explore the mechanism of CHD further.Methods: Polymerase chain reaction-restrict fragment length polymorphism(PCR-RFLP) technique, Polymerase chain reaction-amplied fragment length polymorphism (PCR-AFLP) technique and Polymerase chain reaction-sequence specific primers (PCR-SSP) technique were used to examine the distribution of cytokines gene polymorphisms in patients with CHD and the controls in Hubei province, and gene sequencing was used to confirm the genotypes. ELISA was used in measuring plasma cytokines levels.Results: There are several SNPs (single nucleotide polymorphisms) and one VNTR in cytokines (TNF, IL-1, E-selectin) were confirmed in Chinese Han Population, five single nucleotide mutations in the 5' region of the TNF-a promoter at position -308, -238, -857, -863, -1031, two different polymorphisms in TNF-p at position +252, +804, a single nucleotide polymorphism in IL-1 a at -889, two in IL-1B at -511, +3953, one in IL-IRa at +8006, one VNTR polymorphism in IL-IRa, and two allelic variations in E-selectin at +98, +561 (S128R, also). Genotypes in both cases and controls were in Hardy-Weinberg equilibrium. The distributions of genotypes have significant differences in different races and areas. The results revealed a correlation between polymorphisms at TNF-a -C863A, TNF-p +C804A, E-selectin S128R and coronary heart disease.The frequency of TNF-a -863A allele was lower in CHD than in controls (P<0.01), CC carriers showed an increased risk with an odds ratio of 1.834 for CHD (OR= 1.834, 95%CI= 1.191 ~ 2.823), and -863C carriers showed an...
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