Institute of Genetics and Hospital for Genetic Diseases, OU, Begumpet 500016, India; Dr NTR University of Health Sciences, Vijayawada, India.
Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500082, India.
Epilepsy Res. 2014 Feb;108(2):251-6. doi: 10.1016/j.eplepsyres.2013.11.009. Epub 2013 Nov 17.
Antiepileptic drug (AED) treatment in epilepsy is often compromised by the unpredictability of efficacy and inter-individual variability among patients, which at least in part is the result of genetic variation. The idea to determine an individual's response to a prescribed medicine came into inception around 29 years ago. Pharmacogenetics is used to predict the drug response and efficacy, as well as potential adverse effects. We investigated the functional significance of the C3435T polymorphism of the MDR1 gene in a South Indian population. The patients were divided into responders and non-responders based on their clinical outcome and AED response. The risk of drug resistance was significantly higher in patients bearing TT genotype in comparison to carriers of the homozygous CC genotype [TT vs. CC, χ(2)=12.52; p=0.001, Odds ratio=2.34 (95% CI: 1.942-11.32)]. We suggest that the influence of the C3435T polymorphism in predicting the drug-resistance in epilepsy, might be significant and further investigations focusing on carbamazepine and phenytoin, in various ethnic populations are necessary to clarify the effect of C3435T polymorphism on the multidrug resistance in epilepsy patients.
抗癫痫药物（AED）治疗在癫痫中经常受到疗效的不可预测性和患者个体间变异性的影响，这至少部分是由于遗传变异所致。大约 29 年前，人们开始提出确定个体对规定药物的反应的想法。药物遗传学用于预测药物反应和疗效，以及潜在的不良反应。我们研究了 MDR1 基因 C3435T 多态性在印度南部人群中的功能意义。根据临床结果和 AED 反应将患者分为反应者和非反应者。与纯合 CC 基因型携带者相比，携带 TT 基因型的患者耐药风险明显更高[TT 与 CC， χ(2)=12.52；p=0.001，优势比=2.34（95%CI：1.942-11.32)]。我们建议 C3435T 多态性在预测癫痫耐药性方面的影响可能是显著的，需要进一步研究卡马西平和苯妥英钠在不同种族人群中的作用，以阐明 C3435T 多态性对癫痫患者多药耐药的影响。
