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目的:研究CYP2D6*10基因多态性与美托洛尔治疗高血压疗效的关系。方法:60例原发性高血压患者口服美托洛尔47.5 mg/d三日后,测定口服美托洛尔2h的血药浓度。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CYP2D6*10基因型,根据基因检测结果高血压病人被分为CC型组(野生型纯合子,快代谢型,14例),CT型组(突变杂合子,中代谢型,25例)和TT型组(突变纯合子,弱代谢性,19例)3组。根据CYP2D6*10基因型调整美托洛尔用量,一周后,再次检测口服美托洛尔2h的血药浓度,并检测基因导向治疗前后的平均心率及血压。结果:基因导向治疗前,美托洛尔血药浓度TT组显著高于CC和CT组[(64.74±32.94)ng/ml比(26.57±19.40)ng/ml比(23.88±12.86)ng/ml,P<0.01];与TT组比较,CC组平均收缩压[(132.84±13.40)mmHg比(144.14±14.28)mmHg]、舒张压[(76.95±9.07)mmHg比(81.36±7.33)mmHg]、心率[(69.13±11.83)次/min比(76.66±7.33)次/min]明显升高(P均<0.05)。基因导向治疗后各组的血药浓度、平均收缩压、舒张压及心率无统计学差异(P均>0.05)。与基因导向治疗前比较,CC组治疗后血药浓度显著升高,平均收缩压、舒张压及心率显著降低(P<0.05),CT组、TT组的血压及心率与治疗前比较无统计学差异(P>0.05)。结论:CYP2D6*10基因多态性影响美托洛尔药物代谢及其治疗高血压病的疗效,基因导向个体化治疗可显著改善疗效,短时间内达到理想治疗目标。
Objective: To investigate the relationship between CYP2D6 * 10 gene polymorphism and the efficacy of metoprolol in the treatment of hypertension. Methods: Sixty patients with essential hypertension were treated with metoprolol 47.5 mg / d three days later to determine the plasma concentration of metoprolol orally for 2 hours. CYP2D6 * 10 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to the results of gene test, patients with hypertension were divided into CC group (wild type homozygote, fast metabolizing type, 14 Cases), CT group (mutant heterozygotes, metametabolites, 25 cases) and TT group (homozygous mutant, weak metabolism, 19 cases). According to the CYP2D6 * 10 genotype, the concentration of metoprolol was adjusted. One week later, the concentration of metoprolol orally 2h was tested again and the average heart rate and blood pressure before and after gene therapy were detected. Results: Before gene therapy, the concentration of metoprolol in TT group was significantly higher than that in CC and CT groups [(64.74 ± 32.94) ng / ml vs (26.57 ± 19.40) ng / ml vs (23.88 ± 12.86) ng / ml , P <0.01]. The mean systolic blood pressure (132.84 ± 13.40) mmHg (144.14 ± 14.28) mmHg and diastolic blood pressure (76.95 ± 9.07) mmHg (81.36 ± 7.33) mmHg) Heart rate [(69.13 ± 11.83) times / min (76.66 ± 7.33) times / min] was significantly higher (all P <0.05). There was no significant difference in plasma concentration, mean systolic blood pressure, diastolic blood pressure and heart rate after gene therapy (P> 0.05). Compared with those before gene therapy, the plasma concentration of CC group increased significantly, mean systolic pressure, diastolic pressure and heart rate decreased significantly (P <0.05). There was no significant difference between CT group and TT group in blood pressure and heart rate Difference (P> 0.05). CONCLUSION: CYP2D6 * 10 polymorphism affects the metabolism of metoprolol and its efficacy in the treatment of hypertension. Gene-directed individualized therapy can significantly improve the therapeutic effect and achieve the desired goal in a short period of time.