本文關(guān)鍵詞： 冠心病 CYP17A1基因 單核苷酸多態(tài)性 氯吡格雷抵抗 冠心病 CYP17A1基因 單核苷酸多態(tài)性　出處：《青島大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:冠心病為常見的人類疾病,其發(fā)病率和死亡率均居高不下,隨著全基因組關(guān)聯(lián)分析的發(fā)展,發(fā)現(xiàn)了許多與冠心病相關(guān)的基因,研究較多的是CYP17A1。本研究旨在探討CYP17A1(rs4409766,rs1004467)基因多態(tài)性與冠心病遺傳易感性之間的關(guān)系,擬在基因水平上為冠心病的早期診斷,提供新的思路。方法:選取2014年6月~2016年2月在青島大學(xué)附屬醫(yī)院黃島院區(qū)心血管內(nèi)科住院并行冠狀動(dòng)脈造影診斷為冠心病和非冠心病的患者為研究對象,應(yīng)用實(shí)時(shí)熒光定量PCR(q RT-PCR)技術(shù)對冠心病患者(A組)88例和非冠心病患者(B組)89例,進(jìn)行CYP17A1基因rs4409766,rs1004467的SNP分析,比較基因型頻率及等位基因頻率在2組間的分布,使用SPSS22.0軟件進(jìn)行處理,兩組間數(shù)據(jù)比較采用t檢驗(yàn)或者卡方檢驗(yàn),基因型分布進(jìn)行哈迪-溫伯格遺傳平衡分析,以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:CYP17A1基因rs4409766位點(diǎn)的基因型在A組和B組之間無差別(χ2=5.485,P=0.064,P0.05),rs4409766位點(diǎn)的等位基因頻率分布在兩組中無差異(χ2=0.399,P=0.528,P0.05),但是CC與CT+TT基因型相比較兩組間差異有統(tǒng)計(jì)學(xué)意義(χ2=4.229,P=0.038);rs1004467位點(diǎn)的基因型在A組和B組之間無差別(χ2=2.306,P=0.316,P0.05),rs4409766位點(diǎn)的等位基因頻率分布在兩組中無差異(χ2=0.128,P=0.721,P0.05)。結(jié)論:CYP17A1的rs4409766位點(diǎn)的基因多態(tài)性與冠心病的發(fā)生有關(guān)聯(lián);rs1004467位點(diǎn)的基因多態(tài)性尚不能認(rèn)為與冠心病的發(fā)生有關(guān)聯(lián)。目的:聯(lián)合應(yīng)用氯吡格雷和阿司匹林的抗血小板療法已經(jīng)成為冠心病治療中的常用方案,但是在臨床中出現(xiàn)了由于不同的人群、種族、個(gè)體的不同導(dǎo)致對氯吡格雷的反應(yīng)性存在不同的差異,即有一部分個(gè)體出現(xiàn)了氯吡格雷抵抗或者氯吡格雷低反應(yīng)性,本研究主要探討冠心病患者氯吡格雷抵抗與CYP17A1(rs4409766,rs1004467,rs3824755)基因多態(tài)性之間的關(guān)系。方法:選取2014年6月~2016年10月在青島大學(xué)附屬醫(yī)院黃島院區(qū)心血管內(nèi)科住院并行冠狀動(dòng)脈造影診斷為冠心病的患者169例為研究對象包括氯吡格雷抵抗患者(CR組)52例和氯吡格雷非抵抗患者117例(NCR組),應(yīng)用熒光定量PCR(RT-PCR)技術(shù)對169例患者進(jìn)行CYP17A1基因3位點(diǎn)的SNP分析,比較基因型頻率及等位基因頻率在2組間的分布,使用SPSS22.0軟件進(jìn)行處理,兩組間數(shù)據(jù)比較采用t檢驗(yàn)或者卡方檢驗(yàn),基因型分布進(jìn)行哈迪-溫伯格遺傳平衡分析,以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:CYP17A1基因3個(gè)SNP位點(diǎn)的基因型和等位基因分布在CR組和NCR組之間均無差別(P0.05);結(jié)論:CYP17A1與冠心病患者的氯吡格雷抵抗無關(guān)聯(lián)。
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.4

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