ABCB1基因C3435T多态性对苯巴比妥透过癫痫患者血-脑屏障的影响  

Influence of C3435T polymorphism of ABCB1 gene on penetration of phenobarbital across the blood-brain barrier in patients with epilepsy

作　　者：顾浩 李艺果 赵变歌 陈红莲[2] GU Hao;LI Yiguo;ZHAO Biange;CHEN Honglian(Luohe Second People’s Hospital,Luohe 462000,China;Luohe Medical College,Luohe 462002,China)

机构地区：[1]漯河市第二人民医院,河南漯河462000 [2]漯河医学高等专科学校,河南漯河462002

出　　处：《中国实用神经疾病杂志》2024年第6期711-714,共4页Chinese Journal of Practical Nervous Diseases

基　　金：漯河医专科技创新项目(编号:2023ZD45)。

摘　　要：目的探讨ABCB1基因C3435T多态性对苯巴比妥(PB)透过癫痫患者血-脑屏障(BBB)及癫痫发作的影响。方法选择62例接受PB单药治疗的全身强直-阵挛发作癫痫患者,记录6个月治疗期间的癫痫发作次数。对患者进行ABCB1基因C3435T多态性基因分型,测定脑脊液(CSF)及血清(S)中PB的药物浓度,计算CSF/S-PB浓度比作为PB透过BBB的指标。结果62例患者经ABCB1基因C3435T基因测序分型,其中CC型17例,CT型32例和TT型13例;CC型、CT型和TT型患者CSF-PB分别为(44.71±10.95)μmol/L、(52.75±13.24)μmol/L、(65.64±14.34)μmol/L,CSF/S-PB分别为0.47±0.12、0.53±0.17、0.66±0.19,差异有统计学意义(P<0.05)。CC型发作9次2例,8次1例,7次3例,6次2例,发作超过5次CT型和TT型仅有1例,CC基因型和低CSF/S-PB与癫痫发作频率增加相关(P<0.05)。结论ABCB1基因C3435T多态性显著影响癫痫患者CSF/S-PB浓度比和癫痫发作频率,可能是癫痫耐药的机制之一。Objective To investigate the effect of ABCB1 gene C3435T polymorphism on phenobarbital(PB)penetration across blood-brain barrier(BBB)in vivo and seizure frequency in patients with epilepsy.Methods Sixty-two patients with generalized tonic-clonic seizures who received phenobarbital monotherapy were selected,Seizure frequency was recorded during the 6-month of treatment.The patients were genotyped for the ABCB1 gene C3435T polymorphisms.The concentrations of PB in cerebrospinal fluid(CSF)and serum(S)were measured,CSF/S-PB concentration ratio was calculated as an index of phenobarbital penetration across BBB.Results Sixty-two patients were genotyped by ABCB1 gene C3435T gene sequencing,including 17 cases of CC type,32 cases of CT type and 13 cases of TT type.The CSF-PB of CC,CT and TT patients respectively were(44.71±10.95)μmol/L,(52.75±13.24)μmol/L,(65.64±14.34)μmol/L,CSF/S-PB were 0.47±0.12,0.53±0.17,0.66±0.19,in comparison with CT heterozygotes and TT homozygotes,CC homozygotes had a signifificantly lower CSF-PB concentration(P<0.05)and CSF/S-PB concentration ratio(P<0.05).CC type had 9 seizures in 2 cases,8 seizures in 1 case,7 seizures in 3 cases and 6 seizures in 2 cases,there were more than 5 seizures in 1 case of CT type and TT type,CC genotype and low CSF/S-PB concentration ratio correlated with increased seizure frequency(P<0.05).Conclusion C3435T polymorphism of ABCB1 gene was demonstrated in vivo to signifificantly inflfluence the CSF/S-PB concentration ratio and seizure frequency,it may be one of the mechanisms of drug resistance in epilepsy.

关 键 词：三磷酸腺苷结合盒转运子B亚家族成员1 多态性 耐药性 癫痫 脑脊液 苯巴比妥 

分 类 号：R742.1[医药卫生—神经病学与精神病学]