摘要
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 concentration and adverse reaction of paclitaxel determined using PCR-restriction fragment len concentration of paclitaxel was determined with the relationship of CYP3A5 ＊ 3 gene polymorphism with plasma in ovarian cancer patients. Methods The CYP3A5 genotypes were gth polymorphism in 107 ovarian cancer patients, and the plasma high performance liquid chromatography to analyze the relationship of CYP3A5 ＊ 3 gene polymorphism with plasma concentration and adverse reaction. Results Compared with the wild-type CYP3A5 ＊ 1/＊ 1 carriers, the variant genotypes CYP3A5 ＊ 3/＊ 1 ＋CYP3A5 ＊ 3/＊ 3 carriers had higher incidence of neutropenia and gastrointestinal tract adverse reaction as nausea, vomiting and diarrhea （P~ 0.05）. The patients with variant genotypes had 4.32-fold and 4.08 fold increased risk of neutropenia and gastrointestinal tract adverse reaction, respectively. The variant genotypes carriers had higher 0- and 24-hour plasma concentration than wild-type carriers （P% 0.05）. The incidence of neutropenia was higher in the patients with 24-hour plasma concentration over than 42 /μg/L than that in the patients with 24-hour plasma concentration lower than 42 /μg/L（P〈0.05）. Conclusion CYP3A5 ＊ 3 gene polymorphism may increase the adverse reaction of paclitaxel and is correlated with plasma concentration.
出处
《中华实用诊断与治疗杂志》
2012年第12期1185-1187,共3页
Journal of Chinese Practical Diagnosis and Therapy
关键词
卵巢癌
基因多态性
不良反应
血药浓度
紫杉醇
Ovarian cancer
polymorphism
adverse reaction
plasma concentration
paclitaxel
