【作者】 杨超；

【导师】 李艳；

【作者基本信息】 武汉大学 ， 临床检验诊断学， 2005， 硕士

【摘要】 研究背景 冠心病(coronary heart disease,CHD)是威胁人类身体健康的心血管疾病,其病理基础是动脉粥样硬化(atherosclerosis,AS)。新的研究表明,在AS的病理过程中,炎症起着关键性作用。白细胞介素-6(interleukin-6,IL-6)作为多功能炎症因子,在动脉粥样硬化血管的斑块中可检测到,被证实为心血管疾病风险因子之一,参与AS的形成和发展。大量实验已经证实在IL-6基因启动子上游-174、-634位点存在单核苷酸多态性,可能影响IL-6基因的转录,而IL-6浓度随其基因转录效率不同发生变化,从而影响一些相关疾病发生与发展。因此,IL-6基因多态性的存在会造成个体间对某些疾病的易感性不同。研究IL-6基因多态性与冠心病之间的相关性及其在不同种族间的差异,可以为分子水平研究冠心病的发病机制提供一定参考依据。 目的 1.证实汉族人群存在IL-6基因多态性。 2.证实IL-6基因多态性与冠心病的相关性。 3.IL-6的基因型及血清的表达水平与冠心病的相关性。 方法 运用聚合酶链反应限制性酶切长度多态性分析方法,对202例CHD组患者和189例对照组人群基因组DNA中IL-6基因多态性进行分析,比较IL-6基因多态性在两组间分布及在CHD组不同临床亚组之间IL-6基因型分布的差异性,并分析IL-6不同基因型对冠心病相关临床指标的影响。 结果 1.湖北地区汉族人群中IL-6基因-174G/C多态性位点存在GG、GC二种基因型,其中以GG基因型发生频率最高(97.9%),GC基因型频率次之(2.1%),这种基因多态性分布在男女间差异均无显著性(P>0.05)。与美国、英国人群比较,发现不同种族间IL-6基因型分布及等位基因频率均存在显著差异(P<0.05)。IL-6基因-634C/G多态性位点存在CC、CG和GG三种基因型,其中以CC基因型发生频率最高(66.2%),CG基因型频率次之(31.7%),GG基因型频率最少更多还原

【Abstract】 BackgroundCoronary heart disease (CHD) is one of the most important diseases that threat the population’s health. Pathologic base of CHD is atherosclerosis (AS). Nowadays, atherosclerosis is considered an inflammatory condition. Inflammatory cytokines play key roles in pathologic process in AS. Many researches proved cytokines level were elevated in serum of patients with acute myoeardial infarction or unstable angina. For example, along with other inflammatory markers, elevated levels of interleukin-6 (IL-6), a multifunctional cytokine, were found in patients with unstable angina and with myoeardial infarction. IL-6 takes part in formation and progress of AS with several effects which injury vascular wall and stimulate proliferation of vascular endothelial cells and smooth muscle cells. Recently, two polymorphisms at position -174 (G/C), -634(C/G) of the IL-6 promoter were found to be associated with an increased prevalence of disease. The polymorphisms may influence gene transcription. The level of IL-6 was altered with efficiency variations of gene transcription. Therefore, it can change subjects’ susceptivity to diseases. We think it is important to explore the relation of the IL-6 gene polymorphism with coronary heart disease.ObjectiveThe aim of our study was to investigate the association of the IL-6 SNPs patients with. CHD in Chinese Han population based samples.MethodsIndividuals from Chinese Hubei area samples of CHD patients (total n=202, male=130, female=72) and the population-based survey (189 unselected controls, male=110, female=79) were studied by questionnaire, physical examination, and biochemical analyses. The two polymorphisms were genotyped using PCR-RFLP, compared distribution of IL-6 genotypes in CHD and control group, and that in different CHD clinical situation. Based upon this, we compared clinical indexesassociated with CUD of the IL-6 genotypes, including prevalence rate of hypertension and diabetes mellitus. serum lipid concentration.Results:IL-6 gene-174G/C polymorphism was exiting in normal Hans population of Hubei, the frequency of IL-6 GG genotype was the highest among IL-6 genotypes (97.9%), GC genotype(2.1%), and these gene polymorphisms had no difference between male and female (Z^O.05). Compared with other group, the distributions of IL-6 genotype were significantly different among Occident ethnic groups (P<Q.QS). IL-6 gene -634C/G polymorphism was exiting in normal Hans population of Hubei, the frequency of CC genotype was the highest among IL-6 genotypes (66.2%), CG genotype(31.7%), and these gene polymorphisms had no difference between male and female (P>0.05). Compared with other groups, the distributions of E-selectin genotype were not significantly different among Japanese groups (/><0.05).The genotype frequency of-174 G/C polymorphism of IL-6 gene in CHD group was 99.0% for GG, 1.0% for GC. The genotype distribution of -174 G/C polymorphism of IL-6 gene was not different in CHD patients and controls. The genotype frequency of -634C/G polymorphism of IL-6 gene in CHD group was 46.0% for CC, 34.7% for CG, 19.3% for GG. The analysis of individual genotypes of IL-6 gene -634C/G showed significantly different distributions of genotype and allele between CHD and controls (x2=33.560, PO.001). The relative risk suffered from CHD of CG GG genotype was 1.992 times of the CC genotype(O7? = 1.992, 95%C7 1.324-2.997). The distributions of allele and genotype in IL-6 -634C/G were of significant difference between acute coronary syndrome and stable angina pectoris groups(x"=7.271, Z^O.026). The frequencies of GG genotype and G allele increased gradually in SA, ACS subgroups.Conclusions:There are polymorphisms -174G/C and -634C/G of IL-6 gene in Chinese Han ethnic group. This investigation did not found evidence that the IL-6 -174 G/C promoter polymorphism associates traditional cardiovascular risk factors or theprevalence of CHD in a Chinese sample. The IL-6 -634C/G polymorphism was significant difference between the CHD and controls. The frequency of-634 G allele of IL-6 gene is significant high in CHD than that in controls. The IL-6 -634 C/G mutations maybe associate with a risk of CHD in Han ethnic people.更多还原