Manna Ida, Gambardella Antonio, Labate Angelo, Mumoli Laura, Ferlazzo Edoardo, Pucci Franco, Aguglia Umberto, Quattrone Aldo
Institute of Molecular Bioimaging and Physiology (IBFM), Section of Germaneto, National Research Council, Catanzaro, Italy.
Institute of Neurology, University "Magna Graecia", Germaneto, Catanzaro, Italy.
Seizure. 2015 Jan;24:124-6. doi: 10.1016/j.seizure.2014.09.010. Epub 2014 Oct 2.
A synonymous C to T variant at position 3435 (c.3435C>T) is one common polymorphism of the multidrug resistant 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein. It has been suggested that this polymorphism, and more specifically the 3435CC genotype, may be associated with the response to antiepileptic drug treatment. Here we wished to examine the role of such a candidate variant in a cohort of 175 patients (98 women and 76 men; mean ± SD age: 47.90 ± 17.64) with temporal lobe epilepsy (TLE).
Patients were classified according to whether they had drug-responsive (n=134) or drug-resistant (n=41) epilepsy. We also enrolled 175 healthy controls (93 women and 82 men; mean ± SD age: 72.5 ± 6.8), matched for sex and ethnicity.
Patients and controls were genotyped for detection of the 3435C>T polymorphism, but the analysis showed no significant association between the CC genotype and the risk of drug-resistant epilepsy.
These findings rule out the MDR1 c.3435C>T polymorphism having a major role or increasing the risk of drug-resistance suggesting a revision is required to determine the contribution of this polymorphism in predicting drug response in epilepsy.
3435位（c.3435C>T）的C到T同义变异是多药耐药1（MDR1）基因的一种常见多态性，该基因编码主要的跨膜外排转运体P-糖蛋白。有人提出，这种多态性，更具体地说是3435CC基因型，可能与抗癫痫药物治疗的反应有关。在此，我们希望在175例颞叶癫痫（TLE）患者（98名女性和76名男性；平均±标准差年龄：47.90±17.64）队列中研究这种候选变异的作用。
根据患者癫痫对药物有反应（n=134）或耐药（n=41）进行分类。我们还纳入了175名健康对照者（93名女性和82名男性；平均±标准差年龄：72.5±6.8），并根据性别和种族进行匹配。
对患者和对照者进行基因分型以检测3435C>T多态性，但分析显示CC基因型与耐药性癫痫风险之间无显著关联。
这些发现排除了MDR1基因c.3435C>T多态性起主要作用或增加耐药风险的可能性，提示需要进行修订以确定该多态性在预测癫痫药物反应中的作用。
