ABCC2 rs2273697 and rs3740066 Polymorphisms and Resistance to Antiepileptic Drugs in Asia Pacific Epilepsy Cohorts

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

KEYWORDS::

• drug responsiveness
• epilepsy
• polymorphism

Acknowledgements

The authors gratefully acknowledge the Malaysian, Hong Kong and Japanese patients for their participation in this study, as well as the staff of the hospitals for their assistance in recruiting patients. The authors also thank GP Reynolds, Honorary Professor at Sheffield Hallam University, and D Irwin, Director of Applications and Technology at Sequenom Asia Pacific, for their valuable guidance.

Financial & competing interests disclosure

This study was supported by grant HIR-MOHE E000025-20001, UM PPP grant (PV111/2011A) and RG520-13HTM from Malaysia, Research Grants Council of the Hong Kong Special Administrative Region from China (Project no. CUHK4466/06M) and research grant from Japan (KAKENHI no. 19590539, 16109006 and 22790161). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by grant HIR-MOHE E000025-20001, UM PPP grant (PV111/2011A) and RG520-13HTM from Malaysia, Research Grants Council of the Hong Kong Special Administrative Region from China (Project no. CUHK4466/06M) and research grant from Japan (KAKENHI no. 19590539, 16109006 and 22790161). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.