GSTT1、GSTM1基因多态性与大剂量甲氨蝶呤血药浓度及消化道黏膜损伤的关系研究  

Association between GSTT1 and GSTM1 genes polymorphisms and plasma concentration and gastric mucosal damage induced by methotrexate

作　　者：许静[1] 李庆平[2] 王斌[2] 陆勤[1] 方拥军[1] 黄婕[1] 徐康康[1] 罗琳[1] 

机构地区：[1]南京医科大学附属南京儿童医院,江苏南京210008 [2]南京医科大学基础医学院药理学系,江苏南京210019

出　　处：《安徽医药》2010年第11期1336-1338,共3页Anhui Medical and Pharmaceutical Journal

基　　金：江苏省卫生厅医学科技发展基金临床药学科研项目(No200706)

摘　　要：目的研究谷胱甘肽硫转移酶（Glutathione S-transferases,GSTs）家族中GSTT1、GSTM1基因多态性与急性淋巴细胞白血病患儿甲氨蝶呤（Methotrexate,MTX）血药浓度及消化道黏膜损伤的关系。方法筛选急性淋巴细胞白血病患儿98例,采用多重PCR技术分析GSTT1、GSTM1基因型,运用荧光偏振免疫分析法（FPIA）测定MTX血药浓度,同时观察患儿消化道黏膜损伤情况。结果大剂量甲氨蝶呤（3-5 g·m^-2）致消化道黏膜损伤的发生率为62.24%。相对于GSTT1基因非缺失型患儿,GSTT1基因缺失型患儿MTX 44 h血药浓度较高（P=0.003 9）。GSTM1基因型与甲氨蝶呤44 h血药浓度无明显相关。GSTT1、GSTM1两基因型均与甲氨蝶呤导致的消化道黏膜损伤无明显相关。结论 GSTT1、GSTM1基因多态性可能与MTX消化道黏膜损伤无关,尚不能作为预测HDMTX消化道黏膜损伤的遗传学标记。Aim To investigate the association between GSTT1 and GSTM1 genes polymorphisms and plasma concentration and gastric mucosal damage of high-dose methotrexate（MTX） in children with acute lymphoblastic leukemia（ALL）.Methods GSTT1 and GSTM1 genotypes were analysed in 98 ALL patients with PCR.Fluorescenece polaeization immunoassay（FPIA） was used to determine the plasma concentration of MTX.The toxicity response of the patients was observed.Results Patients without GSTT1 gene had higher plasma MTX concentration than patients with GSTT1 gene（P=0.003 9）.The incidence rate of gastric mucosal damage induced by MTX had no significant correlation with GSTT1 and GSTM1 polymorphisms.Conclusions There is no correlation between GSTT1 and GSTM1 genes polymorphisms and MTX-induced gastric mucosal damage.GSTT1 and GSTM1 genotypes might not be useful in predicting gastric mucosal damage induced by MTX in children with ALL.

关 键 词：谷胱甘肽硫转移酶 多态性 甲氨蝶呤 血药浓度 黏膜损伤 

分 类 号：R733.7[医药卫生—肿瘤]