Pharmacogenomics in epilepsy.
Pharmacogenomics in epilepsy.
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DOI：
10.1016/j.neulet.2017.01.014
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发表时间：
2018-02-22
影响因子：
2.5
通讯作者：
Sisodiya SM
中科院分区：
文献类型：
--
作者：
Balestrini S;Sisodiya SM
遗传变异可以通过各种效应过程影响抗癫痫药物 (AED) 治疗的反应。许多 AED 的代谢是由细胞色素 P450 (CYP) 家族介导的；一些 CYP 具有可能影响血清 AED 浓度的等位基因变异。 “精准医学”侧重于识别潜在的遗传病因，从而实现个性化的治疗选择。某些人类白细胞抗原、HLA、等位基因与特殊药物不良反应的风险增加有关。大规模跨国努力不断涌现新成果，可能很快就会从药物遗传学角度增加有价值的知识。癫痫患者对抗癫痫治疗的反应存在很大差异。遗传因素对这种变异有很大影响。癫痫遗传学和神经生物学的最新进展正在为癫痫治疗的新时代奠定基础，重点关注每个个体及其特定的癫痫。对抗癫痫药物治疗的反应变化可能是由一系列基因类别的遗传变异引起的，包括影响药物药代动力学和药物药效学的基因，但也包括实际上引起癫痫本身的基因。从纯粹的药物遗传学角度来看，在癫痫方面几乎没有可靠的遗传学研究结果和明确的证据。许多发现仍因轶事或不太安全的证据而存在争议，需要进一步验证，例如转运系统和抗癫痫药物靶标的基因变异。基因测序的越来越多的使用和大规模合作项目的结果可能很快就会扩大现有的证据。精准医学治疗代表了越来越多的关注领域，重点是逆转或规避特定基因突变的病理生理效应。通过针对每个特定个体导致癫痫的生物机制，这可能会显着提高癫痫治疗的有效性和安全性。尽管关于癫痫药物遗传学的文章已经很多，但现在似乎正在积聚动力，有望在临床上提供使用结果。
Genetic variation can influence response to antiepileptic drug (AED) treatment through various effector processes. Metabolism of many AEDs is mediated by the cytochrome P450 (CYP) family; some of the CYPs have allelic variants that may affect serum AED concentrations. ‘Precision medicine’ focuses on the identification of an underlying genetic aetiology allowing personalised therapeutic choices. Certain human leukocyte antigen, HLA, alleles are associated with an increased risk of idiosyncratic adverse drug reactions. New results are emerging from large-scale multinational efforts, likely imminently to add knowledge of value from a pharmacogenetic perspective. There is high variability in the response to antiepileptic treatment across people with epilepsy. Genetic factors significantly contribute to such variability. Recent advances in the genetics and neurobiology of the epilepsies are establishing the basis for a new era in the treatment of epilepsy, focused on each individual and their specific epilepsy. Variation in response to antiepileptic drug treatment may arise from genetic variation in a range of gene categories, including genes affecting drug pharmacokinetics, and drug pharmacodynamics, but also genes held to actually cause the epilepsy itself. From a purely pharmacogenetic perspective, there are few robust genetic findings with established evidence in epilepsy. Many findings are still controversial with anecdotal or less secure evidence and need further validation, e.g. variation in genes for transporter systems and antiepileptic drug targets. The increasing use of genetic sequencing and the results of large-scale collaborative projects may soon expand the established evidence. Precision medicine treatments represent a growing area of interest, focussing on reversing or circumventing the pathophysiological effects of specific gene mutations. This could lead to a dramatic improvement of the effectiveness and safety of epilepsy treatments, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Whilst much has been written about epilepsy pharmacogenetics, there does now seem to be building momentum that promises to deliver results of use in clinic.
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DOI：
10.1007/s13311-015-0372-8
发表时间：
2016-01
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Boerma RS;Braun KP;van den Broek MP;van Berkestijn FM;Swinkels ME;Hagebeuk EO;Lindhout D;van Kempen M;Boon M;Nicolai J;de Kovel CG;Brilstra EH;Koeleman BP
通讯作者：
Koeleman BP
影响因子：
30.8
作者：
Carvill, Gemma L.;Regan, Brigid M.;Yendle, Simone C.;O'Roak, Brian J.;Lozovaya, Natalia;Bruneau, Nadine;Burnashev, Nail;Khan, Adiba;Cook, Joseph;Geraghty, Eileen;Sadleir, Lynette G.;Turner, Samantha J.;Tsai, Meng-Han;Webster, Richard;Ouvrier, Robert;Damiano, John A.;Berkovic, Samuel F.;Shendure, Jay;Hildebrand, Michael S.;Szepetowski, Pierre;Scheffer, Ingrid E.;Mefford, Heather C.
通讯作者：
Mefford, Heather C.
影响因子：
5.6
作者：
Barker BS;Ottolini M;Wagnon JL;Hollander RM;Meisler MH;Patel MK
通讯作者：
Patel MK
影响因子：
3.8
作者：
Ceulemans, BPGM;Claes, LRF;Lagae, LG
通讯作者：
Lagae, LG
影响因子：
6.1
作者：
Bechi, Giulia;Rusconi, Raffaella;Mantegazza, Massimo
通讯作者：
Mantegazza, Massimo