Magadmi Rania, Alyoubi Reem, Moshrif Tahani, Bakhshwin Duaa, Suliman Bandar A, Kamel Fatemah, Jamal Maha, Burzangi Abdulhadi S, Basit Sulman
Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pediatric Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Biomedicines. 2023 Sep 11;11(9):2505. doi: 10.3390/biomedicines11092505.
Epilepsy is one of the most common chronic neurodisorders in the pediatric age group. Despite the availability of over 20 anti-seizure medications (ASMs) on the market, drug-resistant epilepsy still affects one-third of individuals. Consequently, this research aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette subfamily B member 1 () gene in epileptic pediatric patients and their response to ASMs. This multicentric, cross-sectional study was conducted among Saudi children with epilepsy in Jeddah, Saudi Arabia. The polymorphism variants of rs1128503 at exon 12, rs2032582 at exon 21, and rs1045642 at exon 26 were genotyped using the Sanger sequencing technique. The study included 85 children with epilepsy: 43 patients demonstrated a good response to ASMs, while 42 patients exhibited a poor response. The results revealed that good responders were significantly more likely to have the TT genotypes at rs1045642 and rs2032582 SNPs compared to poor responders. Additionally, haplotype analysis showed that the T-G-C haplotype at rs1128503, rs2032582, and rs1045642 was only present in poor responders. In conclusion, this study represents the first pharmacogenetic investigation of the gene in Saudi epileptic pediatric patients and demonstrates a significant association between rs1045642 and rs2032582 variants and patient responsiveness. Despite the small sample size, the results underscore the importance of personalized treatment for epileptic patients.
癫痫是儿童年龄组中最常见的慢性神经疾病之一。尽管市场上有20多种抗癫痫药物（ASM），但耐药性癫痫仍影响着三分之一的患者。因此，本研究旨在调查癫痫患儿ATP结合盒亚家族B成员1（）基因的单核苷酸多态性（SNP）与其对ASM反应之间的关联。这项多中心横断面研究是在沙特阿拉伯吉达的癫痫沙特儿童中进行的。使用桑格测序技术对第12外显子的rs1128503、第21外显子的rs2032582和第26外显子的rs1045642的多态性变体进行基因分型。该研究纳入了85名癫痫儿童：43名患者对ASM反应良好，而42名患者反应不佳。结果显示，与反应不佳者相比，反应良好者在rs1045642和rs2032582 SNP处具有TT基因型的可能性显著更高。此外，单倍型分析表明，rs1128503、rs2032582和rs1045642处的T-G-C单倍型仅存在于反应不佳者中。总之，本研究是对沙特癫痫患儿基因的首次药物遗传学研究，证明了rs1045642和rs2032582变体与患者反应性之间存在显著关联。尽管样本量较小，但结果强调了癫痫患者个性化治疗的重要性。
