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The association of ABCB1 gene polymorphism with clinical response to carbamazepine monotherapy in patients with epilepsy

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Abstract

Background

Epilepsy is a common neurological disease but around 30% of patients fail to respond to antiepileptic drug (AED) treatment. Genetic variation of the ATP-binding cassette subfamily B, member 1 (ABCB1) gene, a drug efflux transporter may infer treatment resistance by decreasing gastrointestinal absorption and preventing AED entry into the brain. This study examined the impact of ABCB1 genetic variants on carbamazepine responsiveness.

Materials and methods

Genomic DNA was extracted from whole blood of 104 epileptic patients. Genotyping of 3 ABCB1 variants (c.C3435T, c.G2677T/A and c.C1236T) was undertaken using validated TaqMan allelic discrimination assays. Plasma carbamazepine levels were measured at 3 and 6 months following the initial dose using high-performance liquid chromatography (HPLC) alongside clinical outcomes evaluation.

Results

Nonresponse to carbamazepine (CBZ) was associated significantly with the ABCB1 variants c.C3435T, c.G2677T/A, c.C1236T and TTT, TTC haplotypes (P < 0.05). There was no significant association between variants and plasma CBZ level (P > 0.05).

Conclusions

Our results showed that variant alleles of the ABCB1 gene and TTT, TTC haplotypes were significantly associated with CBZ resistance without affecting the plasma level of carbamazepine. The findings of this study may help to predict patient’s response to treatment ultimately it will improve the personalized and evidence based treatment choice of patients with epilepsy.

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Data availability

The corresponding author will provide the datasets used in the current work upon reasonable request.

Abbreviations

ABC:

ATP-binding cassette

AEDs:

Antiepileptic drugs

BBB:

Blood brain barrier

MDR:

Multi drug resistance

DNA:

Deoxyribonucleic acid

EDTA:

Ethylenediamine-tetra acetic acid

EEG:

Electroencephalography

ASM:

Antiseizure medication

P-gp:

P-glycoprotein

SNP:

Single nucleotide polymorphism

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Acknowledgements

The authors would extend heartfelt graciousness to Professor Sir Munir Pir Mohammed, the University of Liverpool UK, and Higher Education Commission of Pakistan (HEC) for providing opportunity for research work. Additionally, the authors would like to express their appreciation to the Quaid-i-Azam University Islamabad faculty members who supported them throughout the entire research process.

Funding

No funding sources are declared.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan

    Haroon Ur Rashid, Muhammad Imran Asad, Mujeeb Ur Rehman & Muhammad Khalid Tipu

  2. Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan

    Shakir Ullah

  3. Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK

    Daniel F. Carr

  4. Department of Pharmacy, University of Swabi, Anbar, Swabi, 23561, Khyber Pakhtunkhwa, Pakistan

    Muhammad Ijaz Khan Khattak

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  1. Haroon Ur Rashid
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Contributions

HR: collected, processed and analysed patient’s samples and supervised patient’s clinical follow-up, MKT assisted in designing, conceptualizing, writing the manuscript and supervised the research. DC: undertook genotyping and final review of manuscript. SU: helped in Conceptualizing, designing, and providing resources. MIKK: helped in manuscript writing and responsible for resources, MIA, MR are responsible for resources, validation and formal analysis.

Corresponding author

Correspondence to Muhammad Khalid Tipu.

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Conflict of interest

The authors declared no conflict of interest.

Ethical approval

According to protocol number BEC-FBS-QAU2021-342, the study was approved by the Quaid-i-Azam University Islamabad's bioethics committee.

Informed consent

Clear verbal and written information about the study was provided to participants’ parent/guardian in their native language. The recruited patients gave their informed consent voluntarily.

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Rashid, H.U., Ullah, S., Carr, D.F. et al. The association of ABCB1 gene polymorphism with clinical response to carbamazepine monotherapy in patients with epilepsy. Mol Biol Rep 51, 191 (2024). https://doi.org/10.1007/s11033-023-09061-5

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