CYP17A1基因多态性与冠心病的研究

发布时间：2018-02-20 15:10

本文关键词： 冠心病 CYP17A1基因单核苷酸多态性氯吡格雷抵抗冠心病 CYP17A1基因单核苷酸多态性　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:冠心病为常见的人类疾病,其发病率和死亡率均居高不下,随着全基因组关联分析的发展,发现了许多与冠心病相关的基因,研究较多的是CYP17A1。本研究旨在探讨CYP17A1(rs4409766,rs1004467)基因多态性与冠心病遗传易感性之间的关系,拟在基因水平上为冠心病的早期诊断,提供新的思路。方法:选取2014年6月~2016年2月在青岛大学附属医院黄岛院区心血管内科住院并行冠状动脉造影诊断为冠心病和非冠心病的患者为研究对象,应用实时荧光定量PCR(q RT-PCR)技术对冠心病患者(A组)88例和非冠心病患者(B组)89例,进行CYP17A1基因rs4409766,rs1004467的SNP分析,比较基因型频率及等位基因频率在2组间的分布,使用SPSS22.0软件进行处理,两组间数据比较采用t检验或者卡方检验,基因型分布进行哈迪-温伯格遗传平衡分析,以P0.05为差异有统计学意义。结果:CYP17A1基因rs4409766位点的基因型在A组和B组之间无差别(χ2=5.485,P=0.064,P0.05),rs4409766位点的等位基因频率分布在两组中无差异(χ2=0.399,P=0.528,P0.05),但是CC与CT+TT基因型相比较两组间差异有统计学意义(χ2=4.229,P=0.038);rs1004467位点的基因型在A组和B组之间无差别(χ2=2.306,P=0.316,P0.05),rs4409766位点的等位基因频率分布在两组中无差异(χ2=0.128,P=0.721,P0.05)。结论:CYP17A1的rs4409766位点的基因多态性与冠心病的发生有关联;rs1004467位点的基因多态性尚不能认为与冠心病的发生有关联。目的:联合应用氯吡格雷和阿司匹林的抗血小板疗法已经成为冠心病治疗中的常用方案,但是在临床中出现了由于不同的人群、种族、个体的不同导致对氯吡格雷的反应性存在不同的差异,即有一部分个体出现了氯吡格雷抵抗或者氯吡格雷低反应性,本研究主要探讨冠心病患者氯吡格雷抵抗与CYP17A1(rs4409766,rs1004467,rs3824755)基因多态性之间的关系。方法:选取2014年6月~2016年10月在青岛大学附属医院黄岛院区心血管内科住院并行冠状动脉造影诊断为冠心病的患者169例为研究对象包括氯吡格雷抵抗患者(CR组)52例和氯吡格雷非抵抗患者117例(NCR组),应用荧光定量PCR(RT-PCR)技术对169例患者进行CYP17A1基因3位点的SNP分析,比较基因型频率及等位基因频率在2组间的分布,使用SPSS22.0软件进行处理,两组间数据比较采用t检验或者卡方检验,基因型分布进行哈迪-温伯格遗传平衡分析,以P0.05为差异有统计学意义。结果:CYP17A1基因3个SNP位点的基因型和等位基因分布在CR组和NCR组之间均无差别(P0.05);结论:CYP17A1与冠心病患者的氯吡格雷抵抗无关联。
[Abstract]:Objective: coronary heart disease is a common human disease with high morbidity and mortality. With the development of genome-wide association analysis, many genes related to coronary heart disease have been found. The aim of this study was to investigate the association between genetic polymorphism of CYP17A1rs4409766rs1004467and genetic susceptibility to coronary heart disease (CHD). Methods: from June 2014 to February 2016, patients with coronary artery disease (CHD) and non-coronary heart disease (non-CHD) in the Department of Cardiovascular Medicine of Huangdao Hospital, affiliated Hospital of Qingdao University, were selected as the study subjects. The SNP analysis of CYP17A1 gene rs4409766 rs1004467 was performed in 88 patients with coronary heart disease (CHD) group A and 89 patients with non-CHD group B by real-time fluorescence quantitative PCR(q RT-PCR.The distribution of genotype frequency and allele frequency in the two groups were compared and treated with SPSS22.0 software. T test or chi-square test were used to compare the data between the two groups, and the genotypes were analyzed by Hardy Weinberg genetic balance analysis. Results there was no significant difference in allele frequencies between group A and group B in the rs4409766 locus of the 1: CYP17A1 gene (蠂 2 / 5.485) (蠂 2 / 5.485). The allele frequencies of rs4409766 were not significantly different between the two groups (蠂 2 / 0.399P0.528 / P 0.05), but there was no significant difference between the two groups in the genotype distribution of CC and CT (P < 0.05). There was no significant difference in allele frequencies between group A and group B (蠂 ~ 2 / 2.306) (蠂 ~ 2 / 2.306) P = 0.316P 0.05 rs4409766. There was no significant difference in allele frequencies between the two groups (蠂 ~ (20.128) P _ (0.721) P _ (0.05) P _ (0.05)). Conclusion there is an association between the rs4409766 polymorphism of the proportion CYP17A1 and the occurrence of coronary heart disease. Objective: antiplatelet therapy combined with clopidogrel and aspirin has become a common therapy for coronary heart disease. However, there are differences in reactivity to clopidogrel due to different population, race and individual, that is, some individuals have clopidogrel resistance or clopidogrel hyporeactivity. The aim of this study was to investigate the relationship between clopidogrel resistance and polymorphism of CYP17A1 rs4409766rs1004467 rs3824755 in patients with coronary heart disease. Methods: from June 2014 to October 2016, the patients were hospitalized in the Department of Cardiovascular Medicine, affiliated Hospital of Qingdao University, and accompanied by coronary artery disease. One hundred and sixty-nine patients with coronary heart disease diagnosed by angiography, including 52 patients with clopidogrel resistance and 117 patients with non-clopidogrel resistance, were studied for SNP analysis of CYP17A1 gene 3 loci by fluorescence quantitative PCRRT-PCRassay (FQ-PCRT) technique in 169 patients with coronary heart disease (CHD), including 52 patients with clopidogrel resistance and 117 patients with clopidogrel non-resistance. The distribution of genotype frequency and allele frequency between the two groups were compared and processed by SPSS22.0 software. The data of the two groups were compared by t test or chi-square test. The genetic balance of the genotype distribution was analyzed by Hardy Weinberg genetic balance. Results the genotypes and alleles of three SNP loci of the 1: CYP17A1 gene had no difference between CR group and NCR group (P 0.05). Conclusion there is no correlation between the proportion of CYP17A1 and clopidogrel resistance in patients with coronary heart disease.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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