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

Autor: Rashid HU; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan., Ullah S; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Carr DF; Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK., Khattak MIK; Department of Pharmacy, University of Swabi, Anbar, Swabi, 23561, Khyber Pakhtunkhwa, Pakistan., Asad MI; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan., Rehman MU; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan., Tipu MK; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. mktipu@qau.edu.pk.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 Jan 25; Vol. 51 (1), pp. 191. Date of Electronic Publication: 2024 Jan 25.
DOI: 10.1007/s11033-023-09061-5
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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