130名妊娠滋养细胞疾病患者的二氢嘧啶脱氢酶活性分布及其与该酶基因多态性的关系  

Dihydropyrimidine Dehydrogenase Activity and Its Relationship with Dihydropyrimidine Dehydrogenase Genetic Polymorphism in 130 Patients with Gestational Trophoblastic Disease

作　　者：蔡乐[1] 朱珠[1] 万希润[2] 杨秀玉[2] 

机构地区：[1]北京协和医学院-中国医学科学院北京协和医院药剂科,北京100730 [2]北京协和医学院-中国医学科学院北京协和医院妇产科,北京100730

出　　处：《中国药物应用与监测》2009年第6期329-333,共5页Chinese Journal of Drug Application and Monitoring

基　　金：国家自然科学基金资助项目(30640092)

摘　　要：目的:对妊娠滋养细胞疾病患者进行二氢嘧啶脱氢酶(DPD)活性分析,并考察二氢嘧啶脱氢酶基因(DPYD)多态性与DPD活性的关系。方法:选择已确诊为妊娠滋养细胞疾病、使用含氟化嘧啶类药物治疗并签署知情同意书的患者作为化疗组患者;从住院病历中筛选出发生过严重不良反应或因不良反应而停药者,发出随诊函,在患者自愿回访时采集血标本,作为回访组;采用HPLC法测定患者DPD活性(以二氢尿嘧啶/尿嘧啶比值表示,即UH2/U),分析DPD活性分布特点。在前期研究DPYD基因型的基础上,考察DPYD多态性与DPD活性的关系。结果:共有130名妊娠滋养细胞疾病患者参加研究,化疗组105名,回访组25名。化疗组患者的UH2/U比值为(7.91±3.23),回访组比值为(7.46±2.00),均近似呈正态分布,但个体间变异程度较大。携带DPYD*2杂合子变异和C2303A杂合子变异患者的UH2/U比值低于DPD活性均值的70%,表明DPYD*2和C2303A杂合子变异与DPD活性缺乏相关;DPYD*9变异与DPD活性未见明显相关关系。结论:中国妊娠滋养细胞疾病患者中存在与DPD活性缺乏相关的DPYD*2和C2303A突变者,但发生频率可能低于1%;DPYD*9、A720C和A2670C在中国人群中呈多态性分布,但未见与DPD活性降低相关。ABSTRACT Objective： To determine the dihydropyrimidine dehydrogenase （DPD） activity in patients with gestational trophoblastic disease （GTD）, and analyze the relationship of dihydropyrimidine dehydrogenase gene （DPYD） polymorphism and DPD activity. Methods： The patients treated for GTD by fluoropyrimidines-containing regime were enrolled as the treatment group. The patients suffered from severe toxicity with fluoropyrimidines-containing treatment were informed for follow-up group. Blood samples were collected for determining DPD activity. The ratios of dihydrouracil/uracil （UHJU）, which can reflect the DPD activity, were determined by HPLC. DPYD genotype was identified beforehand, and the relationship between DPYD polymorphism and DPD activity was analyzed. Results： Among 130 patients, 105 GTD patients were treated with fluoropyrimidines-containing regime, 25 subjects were follow-up patients. UH2/U ratios in the treatment group and the follow-up group were （7.91 ±3.23） and （7.46 ±2.00）, globally followed a Gaussian distribution, but a large degree of inter-individual variation was observed. The DPD activities of patients with the DPYD^＊2 or C2303A type mutation were lower than 70% of the mean DPD activity. It＇ s suggested that the DPYD^＊2 and C2303A type mutation were associated with DPD activity deficiency. The mean UH2/U ratios in patients with DPYD^＊9 was lower than the mean DPD activity, but there was no significant difference. Conclusion： The DPYD^＊2 and C2303A type mutation which were associated with DPD activity deficiency were found in Chinese GTD patients, but the allelic frequencies of DPYD^＊2 and C2303A were lower than 1%. There was genetic polymorphism of DPYD^＊9, A720C and A2670C, but no correlation with DPD activity deficiency was observed.

关 键 词：二氢嘧啶脱氢酶 基因多态性 酶活性 氟化嘧啶类 妊娠滋养细胞疾病 

分 类 号：R714.2[医药卫生—妇产科学] R450[医药卫生—临床医学]