Department of Clinical Pharmacology, JIPMER, Puducherry, India.
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
Drug Metab Pers Ther. 2023 Mar 1;38(2):191-197. doi: 10.1515/dmpt-2022-0157. eCollection 2023 Jun 1.
Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having a role in the requirement of CBZ maintenance dose. The aim was to study the influence of c.337 T>C and genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy.
Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10% EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of c.337 T>C and , the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between the genotypes and CBZ maintenance dose requirement for dominant and recessive models of and . A value of p<0.05 was considered to be statistically significant.
For (rs 7439366), CT required a higher dose (CT 626 mg/day and TT 523 mg/day) but not found to be significant (p-value 0.167). PWE carrying CT genotype of c.337 T>C had 62 mg higher dose when compared to homozygous mutant CC (590 mg/day for CT and 528 mg/day for CC) but p-value was not found to be significant (p-value 0.835).
The results of our study done in 115 PWE showed there was a lack of association between SNPs of c.337 T>C, and CBZ maintenance dose requirement in Southern part of India and this finding has to be confirmed in a larger sample size.
卡马西平（CBZ）是一种用于局灶性发作性癫痫的一线抗癫痫药物。它在血浆卡马西平水平方面表现出个体间的变异性，并且遗传和非遗传因素都在 CBZ 维持剂量的需求中起作用。目的是研究 c.337 T>C 和遗传多态性对癫痫患者 CBZ 维持剂量需求的影响。
符合条件的是年龄在 15-65 岁之间、接受 CBZ 单药治疗且服用相同维持剂量已达一年的男女癫痫患者。在无菌预防措施下，采集 5 毫升静脉血于 10%EDTA 中。离心后，使用细胞成分提取 DNA 并进行基因分型。对于 c.337 T>C 的三种基因型和，使用方差分析（ANOVA）分析平均卡马西平剂量的差异。使用独立样本 t 检验比较基因型与 CBZ 维持剂量需求，以及和的显性和隐性模型。p<0.05 被认为具有统计学意义。
对于（rs7439366），CT 需要更高的剂量（CT 626mg/天和 TT 523mg/天），但没有发现具有统计学意义（p 值 0.167）。与纯合突变 CC 相比，携带 c.337 T>C CT 基因型的 PWE 剂量高 62mg（CT 为 590mg/天，CC 为 528mg/天），但 p 值没有发现具有统计学意义（p 值 0.835）。
在印度南部进行的 115 例 PWE 的研究结果表明，c.337 T>C、和 SNPs 与 CBZ 维持剂量需求之间没有关联，这一发现需要在更大的样本量中得到证实。
