ABCB1 C3435T基因多态性与新疆癫痫患儿左乙拉西坦血药浓度和临床疗效的相关性研究

Relationship between Multidrug Resistance Gene ABCB1 C3435T Gene Polymorphism and Serum Concentration of Levetiracetam in Children with Epilepsy in Xinjiang

目的初步探讨ABCB1 C3435T基因多态性是否影响新疆癫痫患儿口服左乙拉西坦(levetiracetam,LEV)后的血药浓度、临床疗效和不良反应。方法收集并测定116例口服LEV的新疆癫痫患儿血清药物浓度,采用聚合酶链反应-荧光染色原位杂交法检测其ABCB1 C3435T基因型,分析患儿ABCB1 C3435T基因多态性与其血药浓度、临床疗效与不良反应之间的相关性。结果患儿ABCB1 C3435T的C和T等位基因频率存在显著性差异(χ^2=12.520,P<0.01)。CC型、CT型和TT型患儿的血药浓度结果分别为12.02、13.74和14.53μg·mL^-1,方差分析结果显示,3组之间存在显著性差异(F=3.550,P<0.05)。携带TT型的新疆癫痫患儿LEV血药浓度明显高于CC型和CT型。CC型、CT型和TT型患儿的LEV治疗有效组和无效组的css差异均无统计学意义(P>0.05)。CT型患儿的临床治疗有效率高于CC型和TT型患儿,TT型患儿的不良反应发生率高于CC型和CT型患儿。CC型、CT型和TT型患儿的临床疗效和不良反应存在显著性差异(χ^2=12.870,P<0.01;χ^2=19.292,P<0.01)。结论ABCB1 C3435T基因多态性可能影响新疆癫痫患儿的LEV血药浓度结果、临床疗效和不良反应。

OBJECTIVE To explore the relationship between multidrug resistance gene ABCB1 C3435T gene polymorphism and serum concentration,clinical efficacy and adverse reactions of levetiracetam(LEV)in children with epilepsy in Xinjiang.METHODS The serum concentration of 116 children with epilepsy of in Xinjiang were collected and determined by oral LEV.The ABCB1 C3435T genotype was detected by polymerase chain reaction-fluorescence staining in situ hybridization.The correlation between ABCB1 C3435T gene polymorphism and serum concentration,clinical efficacy and adverse reactions was analyzed.RESULTS The C and T allele frequencies of ABCB1 C3435T in children were significantly different(χ^2=12.520,P<0.01).The serum concentration of CC,CT and TT genotypes were 12.02,13.74 and 14.53μg·mL^-1,respectively.The results of ANOVA showed that there were significant differences among the three groups(F=3.550,P<0.05).The serum concentration of LEV in children with epilepsy in Xinjiang with TT type was significantly higher than that of CC type and CT type.There was no significant difference in css between LEV effective group and ineffective group in CC type,CT type and TT type(P>0.05).The clinical effective rate of CT type was higher than that of CC type and TT type,and the incidence of adverse reactions of TT type was higher than that of CC type and CT type.There were significant differences in clinical efficacy and adverse reactions among CC type,CT type and TT type(χ^2=12.870,P<0.01;χ^2=19.292,P<0.01).CONCLUSION ABCB1 C3435T gene polymorphism may has a effect on the serum concentration,clinical efficacy and adverse reactions of LEV in children with epilepsy in Xinjiang.