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Association of BDNF Polymorphisms with the Risk of Epilepsy: a Multicenter Study

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Abstract

Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese.

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Acknowledgments

We gratefully acknowledge subjects from Malaysia and Hong Kong for their participation in this study, as well as the staff of the hospitals for their assistance in recruiting patients.

Compliance with Ethical Standards

ᅟ

Funding

This study was funded by Malaysian Grants HIR MOHE E000025-20001 and RG 520/13HTM and grants HKU7623/08 M, HKU7747/07 M and CUHK4466/06 M from the Research Grants Council of the Hong Kong Special Administrative Region, China.

Conflict of Interest

The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Lembah Pantai, 59100, Kuala Lumpur, Malaysia

      Hidayati Mohd Sha’ari, Batoul Sadat Haerian & Zahurin Mohamed

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

      Larry Baum

    3. Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

      Hui Jan Tan & Azman Ali Raymond

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

      Mohd Hanip Rafia

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

      Patrick Kwan

    6. Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong, China

      Stacey S. Cherny, Pak Chung Sham & Hongsheng Gui

    7. Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

      Kheng Seang Lim

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    1. Hidayati Mohd Sha’ari
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    Correspondence to Batoul Sadat Haerian or Larry Baum.

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    Hidayati Mohd Sha’ari, Batoul Sadat Haerian and Larry Baum contributed equally to this work.

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    Sha’ari, H.M., Haerian, B.S., Baum, L. et al. Association of BDNF Polymorphisms with the Risk of Epilepsy: a Multicenter Study. Mol Neurobiol 53, 2869–2877 (2016). https://doi.org/10.1007/s12035-015-9150-1

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