ABCC2 rs2273697 and rs3740066 polymorphisms and resistance to antiepileptic drugs in Asia Pacific epilepsy cohorts

Author:

Sha‘ari Hidayati Mohd1,Haerian Batoul Sadat2,Baum Larry3,Saruwatari Junji4,Tan Hui Jan5,Rafia Mohd Hanip6,Raymond Azman Ali5,Kwan Patrick7,Ishitsu Takateru8,Nakagawa Kazuko9,Lim Kheng Seang10,Mohamed Zahurin1

Affiliation:

1. Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

2. Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

3. School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China

4. Division of Pharmacology & Therapeutics, Graduate School of Medical & Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan

5. Department of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

6. Division of Neurology, General Hospital Kuala Lumpur, Kuala Lumpur, Malaysia

7. Division of Neurology, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China

8. Kumamoto Saishunso National Hospital, Kumamoto, Japan

9. Division of Pharmacology & Therapeutics, Graduate School of Medical & Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan and Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan

10. Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Abstract

Aim: To examine the relevance of ABCC2 polymorphisms to drug responsiveness in epilepsy cohorts from the Asia Pacific region. Materials & methods: The rs2273697 and rs3740066 polymorphisms were genotyped in 2056 Malaysian (55%), Hong Kong (32%) and Japanese (13%) epilepsy patients. Results: Significant allele association of rs2273697 was observed in Chinese females with epilepsy, Malaysian Chinese patients with generalized seizure and Japanese patients with partial seizure for the AA versus GG genotype model and Malaysian Chinese patients with generalized seizure for the GA versus GG and autosomal dominant models. Significant association of the rs3740066 allele was observed in Malaysian females of Malay origin with cryptogenic epilepsy and Chinese patients with partial seizure and for genotypes in Malay patients with cryptogenic epilepsy for the CT versus CC and autosomal dominant genotype models. Significant results were observed for all haplotypes, but following Bonferroni correction, only the GT haplotype in Chinese patients remained significant. Conclusion: This study suggests that the GT haplotype might be a risk factor for resistance to medication in Chinese patients. Original submitted 14 August 2013; Revision submitted 25 November 2013

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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