Int J Clin Pharmacol Ther. 2022 Mar;60(3):146-158. doi: 10.5414/CP204045.
Previous clinical studies and meta-analyses have shown controversial results on the association between polymorphism of the gene and anti-epileptic drug (AED) resistance. Based on the fact that sample size and confounding factors could contribute to the inconsistency, we performed an updated meta-analysis by including the most recent studies, and subgroup analysis was conducted to evaluate the effect of confounding factors on the association.
We searched articles in 6 electronic databases including PubMed, Medline, Embase, Web of science, Cochrane Library, CNKI (China National Knowledge Infrastructure) for relevant articles up to June 2020.
The current analysis showed that the C allele of variant was a risk factor for drug resistance in the overall populations (C allele vs. T allele, OR: 1.13; 95% CI: 1.02 - 1.25; p = 0.02) and in the Caucasians (C allele vs. T allele, OR: 1.09; 95% CI: 1.09 - 1.43; p = 0.002), while no association was observed in Asians and Indians. Particularly, our study reported for the first time that the 3435T allele was more common in epilepsy patients with drug resistance in the Tunisian population (C allele vs. T allele, OR: 0.31; 95% CI: 0.15 - 0.65; p = 0.002). In addition, our present analysis suggested an association between and AED resistance in cryptogenic, symptomatic, but not in idiopathic patients. Subgroup studies based on age and gender showed no association.
AED resistance in Caucasian and Tunisian populations may benefit from genotyping. We recommend that more details, such as gender and etiology of epilepsy, should be taken into account to draw a reliable conclusion in future studies.
先前的临床研究和荟萃分析表明,基因多态性与抗癫痫药物(AED)耐药之间的关联存在争议。基于样本量和混杂因素可能导致结果不一致的事实,我们进行了一项更新的荟萃分析,纳入了最新的研究,并进行了亚组分析,以评估混杂因素对相关性的影响。
我们在 6 个电子数据库(包括 PubMed、Medline、Embase、Web of science、Cochrane Library、CNKI(中国国家知识基础设施))中搜索了截至 2020 年 6 月的相关文章。
目前的分析表明,变体的 C 等位基因是总体人群(C 等位基因与 T 等位基因,OR:1.13;95%CI:1.02-1.25;p=0.02)和白种人群(C 等位基因与 T 等位基因,OR:1.09;95%CI:1.09-1.43;p=0.002)中药物耐药的危险因素,而在亚洲人和印度人中则没有观察到相关性。特别是,我们的研究首次报道,3435T 等位基因在突尼斯人群中耐药性癫痫患者中更为常见(C 等位基因与 T 等位基因,OR:0.31;95%CI:0.15-0.65;p=0.002)。此外,我们目前的分析表明,与隐匿性、症状性但不是特发性患者的 AED 耐药之间存在关联。基于年龄和性别进行的亚组研究表明没有相关性。
白种人和突尼斯人群的 AED 耐药可能受益于基因分型。我们建议,在未来的研究中应考虑更多细节,如癫痫的性别和病因,以得出可靠的结论。