Table Info

Table 2.

Genetic polymorphism and drug transporters

Drug transporters	Genetic polymorphisms	Implications	Reference(s)
ABCB1 (P-glycoprotein)	3435C>T	Associated with varying drug transportation activity, impacting drug response for carbamazepine and lamotrigine. Significant role in carbamazepine metabolism and resistance; T allele carriers show significantly different carbamazepine plasma levels. Influence on anticonvulsant drug efflux from brain tissue, potentially contributing to drug resistance; CC genotype associated with higher efflux.	[18–21]
EPHX1	c.416A>G	Linked to carbamazepine metabolism, specifically conversion to carbamazepine-10,11-trans-dihydrodiol (CBZD).	[19]

Declarations

Author contributions

AS: Conceptualization, Writing—original draft. KH: Writing—original draft, Writing—review & editing. A Zafar: Validation, Writing—review & editing. A Zainab: Conceptualization, Writing—original draft, Writing—review & editing. SA: Conceptualization, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Kaneko S, Iwasa H, Okada M. Genetic identifiers of epilepsy. Epilepsia. 2002;43:16–20. [DOI] [PubMed]

McCormick DA, Contreras D. On the cellular and network bases of epileptic seizures. Annu Rev Physiol. 2001;63:815–46. [DOI] [PubMed]

Balestrini S, Sisodiya SM. Pharmacogenomics in epilepsy. Neurosci Lett. 2018;667:27–39. [DOI] [PubMed] [PMC]

Smolarz B, Makowska M, Romanowicz H. Pharmacogenetics of Drug-Resistant Epilepsy (Review of Literature). Int J Mol Sci. 2021;22:11696. [DOI] [PubMed] [PMC]

Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020;72:606–38. [DOI] [PubMed] [PMC]

Gambardella A, Labate A, Mumoli L, Lopes-Cendes I, Cendes F. Role of Pharmacogenomics in Antiepileptic Drug Therapy: Current Status and Future Perspectives. Curr Pharm Des. 2017;23:5760–5. [DOI] [PubMed]

Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393:689–701. [DOI] [PubMed]

Kidd RS, Curry TB, Gallagher S, Edeki T, Blaisdell J, Goldstein JA. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics. 2001;11:803–8. [DOI] [PubMed]

Cárdenas-Rodríguez N, Carmona-Aparicio L, Pérez-Lozano DL, Ortega-Cuellar D, Gómez-Manzo S, Ignacio-Mejía I. Genetic variations associated with pharmacoresistant epilepsy (Review). Mol Med Rep. 2020;21:1685–701. [DOI] [PubMed] [PMC]

10.

Božina N, Sporiš IŠ, Božina T, Klarica-Domjanović I, Tvrdeić A, Sporiš D. Pharmacogenetics and the treatment of epilepsy: what do we know? Pharmacogenomics. 2019;20:1093–101. [DOI] [PubMed]

11.

Poor SR, Ettcheto M, Cano A, Sanchez-Lopez E, Manzine PR, Olloquequi J, et al. Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment. Pharmaceuticals (Basel). 2021;14:890. [DOI] [PubMed] [PMC]

12.

Vezzani A, Friedman A, Dingledine RJ. The role of inflammation in epileptogenesis. Neuropharmacology. 2013;69:16–24. [DOI] [PubMed] [PMC]

13.

Gao B, Wu Y, Yang YJ, Li WZ, Dong K, Zhou J, et al. Sinomenine exerts anticonvulsant profile and neuroprotective activity in pentylenetetrazole kindled rats: involvement of inhibition of NLRP1 inflammasome. J Neuroinflammation. 2018;15:152. [DOI] [PubMed] [PMC]

14.

Yoon HY, Ahn MH, Yee J, Lee N, Han JM, Gwak HS. Influence of CYP2C9 and CYP2A6 on plasma concentrations of valproic acid: a meta-analysis. Eur J Clin Pharmacol. 2020;76:1053–8. [DOI] [PubMed]

15.

Dagenais R, Wilby KJ, Elewa H, Ensom MHH. Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region. Drugs R D. 2017;17:341–61. [DOI] [PubMed] [PMC]

16.

Liao K, Liu Y, Ai CZ, Yu X, Li W. The association between CYP2C9/2C19 polymorphisms and phenytoin maintenance doses in Asian epileptic patients: A systematic review and meta-analysis. Int J Clin Pharmacol Ther. 2018;56:337–46. [DOI] [PubMed]

17.

Wu X, Yang H, Waugh DW, Orbe C, Tilmes S, Lamarque JF. Spatial and temporal variability of interhemispheric transport times. Atmos Chem Phys. 2018;18:7439–52. [DOI]

18.

Siddiqui A, Kerb R, Weale ME, Brinkmann U, Smith A, Goldstein DB, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med. 2003;348:1442–8. [DOI] [PubMed]

19.

Eichhorn A, Neumann F, Bäumler C, Gutsmann I, Grobe O, Schlüter F, et al. Assessment of the Diagnostic Performance of Fully Automated Hepatitis E Virus (HEV) Antibody Tests. Diagnostics (Basel). 2024;14:602. [DOI] [PubMed] [PMC]

20.

Fan YX, Zhang Z, Meng JR, Yin SJ, Wang P, Zhou T, et al. Association of ABCB1 polymorphisms with carbamazepine metabolism and resistance in epilepsy: A meta-analysis. Epilepsy Res. 2021;177:106785. [DOI] [PubMed]

21.

Bournissen FG, Moretti ME, Juurlink DN, Koren G, Walker M, Finkelstein Y. Polymorphism of the MDR1/ABCB1 C3435T drug-transporter and resistance to anticonvulsant drugs: a meta-analysis. Epilepsia. 2009;50:898–903. [DOI] [PubMed]

22.

Haerian BS, Roslan H, Raymond AA, Tan CT, Lim KS, Zulkifli SZ, et al. ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: a systematic review and meta-analysis. Seizure. 2010;19:339–46. [DOI] [PubMed]

23.

Li M, Zhong R, Lu Y, Zhao Q, Li G, Lin W. Association Between SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 Polymorphisms and Responsiveness to Antiepileptic Drugs: A Meta-Analysis. Front Neurol. 2021;11:591828. [DOI] [PubMed] [PMC]

24.

Khatri A, Singh VK, Prasad R, Kumar A, Singh VK, Joshi D. In Silico Functional Network Analysis for the Identification of Novel Target Associated with SCN1A Gene. Biomed Biotechnol Res J. 2023;7:163–9. [DOI]

25.

Zhu LN, Chen D, Xu D, Tan G, Wang HJ, Liu L. Newer antiepileptic drugs compared to levetiracetam as adjunctive treatments for uncontrolled focal epilepsy: An indirect comparison. Seizure. 2017;51:121–32. [DOI] [PubMed]

26.

Chen P, Yan Q, Xu H, Lu A, Zhao P. The effects of ABCC2 G1249A polymorphism on the risk of resistance to antiepileptic drugs: a meta-analysis of the literature. Genet Test Mol Biomarkers. 2014;18:106–11. [DOI] [PubMed] [PMC]

27.

Li H, Wang B, Chang C, Wu M, Xu Y, Jiang Y. The roles of variants in human multidrug resistance (MDR1) gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies. PLoS One. 2015;10:e0122043. [DOI] [PubMed] [PMC]

28.

Qian L, Fang S, Yan YL, Zeng SS, Xu ZJ, Gong ZC. The ABCC2 c.-24C>T polymorphism increases the risk of resistance to antiepileptic drugs: A meta-analysis. J Clin Neurosci. 2017;37:6–14. [DOI] [PubMed]

29.

Wang ZJ, Chen J, Chen HL, Zhang LY, Xu D, Jiang WT. Association between SCN1A polymorphism rs3812718 and valproic acid resistance in epilepsy children: a case-control study and meta-analysis. Biosci Rep. 2018;38:BSR20181654. [DOI] [PubMed] [PMC]

30.

Reif PS, Tsai MH, Helbig I, Rosenow F, Klein KM. Precision medicine in genetic epilepsies: break of dawn? Expert Rev Neurother. 2017;17:381–92. [DOI] [PubMed]

31.

Zimmern V, Minassian B, Korff C. A Review of Targeted Therapies for Monogenic Epilepsy Syndromes. Front Neurol. 2022;13:829116. [DOI] [PubMed] [PMC]

32.

Xu D, Chen S, Yang J, Wang X, Fang Z, Li M. Precision therapy with quinidine of KCNT1-related epileptic disorders: A systematic review. Br J Clin Pharmacol. 2022;88:5096–112. [DOI] [PubMed]

33.

Kuersten M, Tacke M, Gerstl L, Hoelz H, Stülpnagel CV, Borggraefe I. Antiepileptic therapy approaches in KCNQ2 related epilepsy: A systematic review. Eur J Med Genet. 2020;63:103628. [DOI] [PubMed]

34.

Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, Lohitnavy M, Tassaneeyakul W. Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2013;149:1025–32. [DOI] [PubMed]

35.

Grover S, Kukreti R. HLA alleles and hypersensitivity to carbamazepine: an updated systematic review with meta-analysis. Pharmacogenet Genomics. 2014;24:94–112. [DOI] [PubMed]