Role of ABCB1 C3435T Variant in Response to Antiepileptic Drugs in Epilepsy: A Review

Role of ABCB1 C3435T Variant in Epilepsy
Vol. 4 No. 2 : 2009 (64-75)

Haerian BS Haerian BS
Mohamed Z Mohamed Z
Mohamed EHM Mohamed EHM
Lim KS Lim KS
Tan HJ Tan HJ
Tan CT Tan CT
Raymond AA Raymond AA

Abstract
Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area.
Keywords : ABCB1, antiepileptic drugs, drug responsiveness, epilepsy, P-gp, pharmacoresistance, single nucleotide polymorphism,
Abstrak
Pengekspresan terlampau P-glikoprotin (P-gp), hasil bagi gen untuk kaset pengikatan ATP (ABC), subfamili B, ahli 1 (ABCB1/MDR1), memain peranan penting dalam mem­perantarai ketahanan multidrug terhadap dadah antiepilepsi (DAE), pada lebih kurang 30% daripada pesakit epilepsi. Variasi genetik mungkin merupakan sebahagian dari­pada sebab kenapa terdapatnya perbezaan inter-individu dalam perhubungan fenotip-genotip bagi respons farmakologikal pesakit epilepsi terhadap DAE. Sinonim poly­morfisme C3435T adalah satu daripada varian alel yang paling kerap berlaku pada gen ABCB1/MDR1, dan ini  dicadangkan sebagai penyebab epilepsi refraktori. Banyak kajian telah menunjukkan hubungan antara polimorfisme C3435T dan refraktori terha­dap DAE bagi penyakit epilepsi. Walaupun begitu, terdapat kontroversi antara hasil penemuan dari pelbagai kajian, iaitu, sama ada  polimorfisme gen ABCB1/MDR1 C3435T berkait dengan respons terhadap DAE bagi pesakit epilepsi. Kertas ulasan ini memberikan latarbelakang dan membincangkan hasil penyiasatan pada faktor-faktor yang bercanggah yang mempengaruhi interpretasi dan implementasi kajian-kajian asosiasi dalam bidang ini.
Kata Kunci : ABCB1, dadah antiepileptik, epilepsi, ketahanan dadah, P-gp, polimorfisme nukleotid tunggal, respons terhadap dadah,

Correspondance Address
Prof Dr Raymond Azman Ali, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur. Email: raymond@ppukm.ukm.my