ABCB1和ABCG2基因多态性与急性药物中毒性脑病的相关研究

Correlation of ABCB1 and ABCG2 gene polymorphisms and acute toxic encephalopathy caused by cancer chemotherapy

目的探讨ABCBl（MDRl）和ABCG2（BCRP）基因的多态性与化疗药物引起中毒性脑病发生的相关性。方法本试验采用单碱基延伸方法对275例急性淋巴系白血病患者ABCBl和ABCG2基因的多态性进行检测，并观察不同基因组合后急性中毒性脑病的发生率。结果ABCBl和ABCG2基因多态性一共包括了ABCBl3435T’C、2677G’T／A、1236C’T和ABCG2421C’A、34G′A基因型。其中ABCB13435TT基因型的病例较3435CC／CT组病例的脑病发病率更高（OR=3．5，P=0．03）。具有ABCG2421A等位基因的病例较野生型纯合子病例的脑病发病率更高（OR=2．0，P=0．25）。有两个致病基因的患者脑病发病率会明显提高（OR=12．3，P=0．005）。结论基因的变异与在化疗过程中发生的急性神经毒性有关。

Objective To study the correlation between ABCB1 （MDR1） and ABCG2 （BCRP） gene polymorphism and toxic encephalopathy caused by chemotherapy drugs. Methods This study used a single nucleotide polymorphism extension method to detect ABCB1 and ABCG2 gene polymorphism in 275 cases of acute lymphoblastic leukemia, and observed the incidence of acute poisoning encephalopathy of different gene combinations. Results The gene polymorphism of ABCB1 in patients consists of 3435T′C, 2677G′ T/A and 1236C′T, and gene polymorphism of ABCG2 consists of 421C′ A and 34G′A. The incidence of encephalopathy was higher in the patients with ABCB1 3435T1＂ genotype than that in the cases with 3435CC/CT genotype （ OR = 3.5, P = 0.03）. The patients with ABCG2 421A alleles had a higher Hino Ojuriko case encephalopathy rate than the patients of wild type （OR =2.0, P = O. 25）. Only one gene mutation （ABCB1 343533′ or ABCG2 421AA/AC） did not increase the risk of encephalopathy, but two mutations together increased encephalopathy risk significantly （ OR = 12.3, P = 0. 005 ）. Conclusion Mutations in these genes associate with acute neurotoxicity occurred in the course of chemotherapy.