Background: The aim of this study was to evaluate whether the voltage-gated sodium channel alpha subunit 1 (SCN1A) gene polymorphisms influence the responsiveness of Jordanian epileptic patients to antiepileptic drugs (AEDs).
Methods: A total of 72 AEDs-treated epileptics were polymerase chain reaction (PCR)-genotyped for six single nucleotide polymorphisms (SNPs), including SCN1A rs2298771, rs3812718, rs3812719, rs2217199, rs2195144 and rs1972445. Genotype and allele distributions in drug-responsive and drug-resistant patients were compared. The six SNPs haplotypes were examined, and the linkage disequilibrium (LD) was assessed.
Results: The genotypes of drug-resistant and drug-responsive groups were in Hardy-Weinberg equilibrium. Three genetic polymorphisms of the SCN1A gene seemed to influence the resistance to AEDs, on the level of alleles and genotypes. Data revealed that rs2298771 G allele, rs3812719 C allele, and rs2195144 T allele increased the risk of developing AEDs-resistance (OR=2.9; 95%CI= 1.4-5.9, p=0.003; OR=2.4; 95%CI=1.2-4.7, p=0.01; OR=2.3; 95%CI=1.2-4.7, p=0.01), respectively. Haplo type analysis of SCN1A polymorphisms revealed high-degree LD associated with resistance to AEDs. A synergetic effect appears with highly significant association in GCCATG haplotype of rs2298771, rs3812718, rs3812719, rs2217199, rs2195144, and rs1972445 respectively (OR=2.8; 95%CI=1.5-6.2, p=0.002).
Conclusions: Data suggests that SCN1A polymorphisms could influence the resistance to AEDs in Jordanian epileptics at three SNPs (rs2298771; rs3812719; rs2195144). Additionally, haplotype analysis indicated a substantial degree of LD between the six SCN1A polymorphisms. Further investigation with larger sample size is needed to confirm the results of the current study.
Uvod: Cilj ove studije bio je da se proceni da li polimorfizmi gena alfa podjedinice 1 natrijumovog kanala (SCN1A) utiču na reakciju na antiepileptičke lekove (AED) kod epileptičnih pacijenata u Jordanu.
Metode: Ukupno 72 pacijenta sa epilepsijom koji su tretirani sa AED su bili genotipizovani polimerazom lančane reakcije (PCR) za šest pojedinačnih nukleotidnih polimorfizama (SNP), uključujući SCN1A rs2298771, rs3812718, rs3812719, rs2217199, rs2195144 i rs1972445. Poređene su distribucije genotipa i alela kod pacijenata koji reaguju na lekove i pacijenata koji su rezistentni na lekove. Ispitano je šest haplotipova SNP-a i procenjena je neravnoteža veze (LD).
Rezultati: Genotipovi grupa otpornih na lekove i grupa koje reaguju na lekove su bili u Hardy-Weinberg-ovoj ravnoteži. Činilo se da tri genetska polimorfizma gena SCN1A utiču na otpornost na AED, na nivou alela i genotipova. Podaci su otkrili da alel rs2298771 G, alel rs3812719 C i alel rs2195144 T povećavaju rizik od razvoja rezistencije na AED (OR=2,9; 95%CI=1,4-5,9, p=0,003; OR=2,4; 95%CI= 95%CI=1,2-4,7, p=0,01; OR=2,3; 95% CI=1,2-4,7, p=0,01), respektivno. Analiza haplotipa polimorfizama SCN1A otkrila je LD visokog stepena povezanu sa otpornošću na AED. Sinergetski efekat se pojavljuje sa visoko značajnom asocijacijom u GCCATG haplotipu rs2298771, rs3812718, rs3812719, rs2217199, rs2195144 i rs1972445, respektivno (OR=2,8; 95%CI=1,5-6,2, p=0,002).
Zaključak: Podaci ukazuju da bi polimorfizmi SCN1A mogli da utiču na otpornost na AED kod pacijenata iz Jordana sa epilepsijom kod tri SNP (rs2298771, rs3812719, rs2195144). Pored toga, analiza haplotipa je ukazala na značajan stepen LD između šest SCN1A polimorfizama. Potrebno je dalje istraživanje na većem uzorku da bi se potvrdili rezultati trenutne studije.
Keywords: SCN1A polymorphisms; antiepileptic drugs; drug resistance; epilepsy.
2023 Rami Abduljabbar, Tamimi Duaa Eid, Al-Motassem Yousef, Saeed Ramzi Mukred, Mohammed Zawiah, published by CEON/CEES.