冠心病患者CYP2C19基因型检测与光学比浊法测定血小板聚集率的相关性研究

发布时间：2018-04-25 09:35

本文选题：CYP2C19 + 氯吡格雷　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:分析冠心病患者CYP2C19基因型检测与经氯吡格雷治疗前后通过光学比浊法测定血小板聚集率的相关性。方法:入选自2016年2月至2017年2月期间、河北医科大学第二医院心血管内五科收治的冠心病患者。患者入院前未接受任何抗血小板治疗,入院给予300mg氯吡格雷+300mg阿司匹林负荷量后,以75mg氯吡格雷+100mg阿司匹林每天持续治疗。分别以光学比浊法检测患者服用氯吡格雷抗血小板治疗前与治疗3天后的血小板聚集率。所有患者均以荧光染色原位杂交法定性检测CYP2C19基因型。根据CYP2C19基因型检测结果及所支配的酶分为三种不同的代谢类型:正常代谢型(RM,*1/*1)、慢代谢型(PM,*2/*2,*2/*3,*3/*3),中间代谢型(IM,*1/*2,*1/*3,*17/*2,*17/*3)。通过光学比浊法检测血小板聚集率变化,将两次血小板聚集率均50%的患者定义为高反应组,第二次血小板聚集率下降至50%,定义为反应正常组,观察两组患者指标:年龄、性别、体重指数、血小板计数、血红蛋白计数、左室射血分数、合并糖尿病、高血压、血脂异常等疾病、吸烟、PPI用药史等。统计分析采用SPSS 21.0软件,应用二元logistic回归分析氯吡格雷药物治疗后反应性与代谢基因型的相关性。将双侧P0.05视为有差异有统计学意义。结果:1本试验共纳入患者46例,其中女性患者15(32.6%)例,男性患者31例(67.4%),年龄36-75岁,平均为58.8±9.5,吸烟患者21例(45.6%),高血压患者33例(71.7%),糖尿病患者18例(39.1%),血脂异常患者25例(54.3%)。对所有患者进行CYP2C19基因型检测,其中正常代谢型患者22例(47.8%),中间代谢型15例(32.6%),慢代谢型患者9人(19.5%),药物反应正常组33人(71.7%),高反应性组13人(28.3%)。2入院时,正常代谢型组患者血小板聚集率水平为86.4±6.7%,中间代谢型组为87.9±4.8%,慢代谢型组为89.8±3.2%,三组数据统计学无差异(P0.05)。用药3天后,正常代谢型组的血小板聚集率为34.8±8.2%,中间代谢型组为45.4±5.8%,慢代谢型组为64.0±5.5%,三组数据统计学上有差异(P0.05)。3氯吡格雷药物治疗后,高反应性组和反应正常组两组患者在年龄、性别、体重指数、血小板计数、合并糖尿病、高血压、血脂异常、吸烟,PPI用药等方面两者并无统计学差异(All P0.05)。4在三种代谢型中,反应正常的患者和高反应性患者数量具有差异,且差异具有统计学意义(P0.05);二元Logistic回归分析药物反应性与代谢基因型的相关性,结果显示,患者药物治疗后反应性与CYP2C19基因型检测具有相关性(P=0.01,OR=10.096)。结论:光学比浊法测定血小板聚集率与CYP2C19代谢基因型检测具有显著相关性。
[Abstract]:Objective: to analyze the correlation between CYP2C19 genotypes and platelet aggregation by optical turbidimetry before and after clopidogrel treatment. Methods: patients with coronary heart disease were selected from February 2016 to February 2017. The patient received no antiplatelet therapy before admission and continued daily treatment with 75mg clopidogrel 100mg aspirin after admission to 300mg clopidogrel 300mg aspirin load. The platelet aggregation rate was measured by optical turbidimetry before and 3 days after antiplatelet therapy with clopidogrel. CYP2C19 genotypes were detected qualitatively by fluorescence staining in situ hybridization in all patients. According to the results of CYP2C19 genotypic analysis and the controlled enzymes, there are three different metabolic types: the normal metabolic type is 1 / 1 / 1, the slow metabolic type is 2 / 2 / 2 / 10 / 3 / 3, and the intermediate metabolic type is 1 / / 2 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 2 / 3 / 3 / 3 / 3 / 3 / 3 / 2 / 3 / 3 / 3 / 3 The change of platelet aggregation rate was determined by optical turbidimetry. The patients with 50% platelet aggregation rate at both times were defined as high reaction group, and the second platelet aggregation rate was reduced to 50. The second platelet aggregation rate was defined as the normal reaction group. Body mass index, platelet count, hemoglobin count, left ventricular ejection fraction, diabetes mellitus, hypertension, dyslipidemia, smoking history of PPI. SPSS 21.0 software was used to analyze the correlation between reactivity and metabolic genotype by binary logistic regression analysis after clopidogrel treatment. There was significant difference between the two sides. Results A total of 46 patients were included in the study, including 153.66 female patients and 31 male patients with a mean age of 58.8 卤9.5 years, aged 36-75 years, 21 patients with smoking, 33 patients with hypertension, 33 patients with hypertension, 39.1patients with diabetes mellitus, 25 patients with dyslipidemia and 54.3patients with dyslipidemia. CYP2C19 genotypes were detected in 22 patients with normal metabolic type, 15 patients with intermediate metabolic type, 9 patients with slow metabolic type, 33 patients with normal drug reaction, and 13 patients with hyperreactivity. The platelet aggregation rate was 86.4 卤6.7in the normal metabolic type group, 87.9 卤4.8 in the intermediate metabolic type group and 89.8 卤3.2 in the slow metabolic type group. There was no statistical difference among the three groups (P 0.05). After 3 days treatment, the platelet aggregation rate was 34.8 卤8.2 in the normal metabolic type group, 45.4 卤5.8 in the intermediate metabolic type group and 64.0 卤5.5 in the slow metabolic type group. There was no significant difference in sex, body mass index, platelet count, diabetes mellitus, hypertension, dyslipidemia, smoking and PPI use. Among the three metabolic types, there were significant differences in the number of patients with normal reaction and those with hyperreactivity. The correlation between drug reactivity and metabolic genotype was found by binary Logistic regression analysis. The results showed that there was a correlation between drug reactivity and CYP2C19 genotypes after drug therapy. Conclusion: optical turbidimetry has a significant correlation with CYP2C19 metabolic genotypes.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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