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目的探讨卵巢癌患者代谢酶CYP3A5*3基因多态性与紫杉醇血药浓度及不良反应的相关性。方法107例卵巢癌患者,采用聚合酶链反应-限制性片段长度多态性技术检测患者的CYP3A5*3基因型,采用高效液相色谱法测定患者紫杉醇血药浓度,分析CYP3A5*3变异基因型与血药浓度及不良反应的相关性。结果携有变异基因型(CYP3A5*3/*1+CYP3A5*3/*3)者使用紫杉醇后恶心、呕吐、腹泻以及中性粒细胞减少的发生率高于携有野生基因型(CYP3A5*1/*1)者(P<0.05),且发生风险分别是野生基因型携有者的4.32倍和4.08倍;0,24h时CYP3A5*3变异基因型携带者紫杉醇血药浓度明显高于野生型基因者(P<0.05);24h紫杉醇血药浓度>42μg/L者中性粒细胞减少发生率高于≤42μg/L者(P<0.05)。结论 CYP3A5*3基因多态性可能增加紫杉醇不良反应,并与高血药浓度有关。
Objective To investigate the relationship between polymorphism of CYP3A5 * 3 gene and paclitaxel blood concentration and adverse reactions in patients with ovarian cancer. Methods One hundred and seven patients with ovarian cancer were enrolled in this study. The CYP3A5 * 3 genotype was detected by polymerase chain reaction - restriction fragment length polymorphism (PCR - RFLP). The plasma concentration of paclitaxel was determined by high performance liquid chromatography (HPLC) Correlation with plasma concentration and adverse reactions. Results The incidence of nausea, vomiting, diarrhea and neutropenia after using paclitaxel was higher in patients with variant genotypes (CYP3A5 * 3 / * 1 + CYP3A5 * 3 / * 3) / * 1) (P <0.05), and the risk was 4.32-fold and 4.08-fold higher than that of the wild type carriers; at 0 and 24 h, the plasma concentration of paclitaxel in CYP3A5 * 3 variant genotypes was significantly higher than that in the wild type (P <0.05). The incidence of neutropenia in patients receiving paclitaxel at a concentration of 42μg / L for 24 h was higher than that of patients receiving less than 42μg / L (P <0.05). Conclusion CYP3A5 * 3 gene polymorphism may increase paclitaxel adverse reactions, and with high plasma concentration.