Zhao Gui-Xin, Zhang Zheng, Cai Wen-Ke, Shen Ming-Li, Wang Ping, He Gong-Hao
Department of Pharmacy, 920th Hospital of Joint Logistics Support Force, Kunming, 650032, China; Kunming Medical University, Kunming, 650500, China; Research Center of Clinical Pharmacology, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, 650021, China.
Medical Engineering Section, The 306th Hospital of PLA, Beijing, 100101, China.
Epilepsy Res. 2021 Jul;173:106615. doi: 10.1016/j.eplepsyres.2021.106615. Epub 2021 Mar 17.
CYP3A4 (rs2242480), CYP3A5 (rs776746) and SCN1A (rs3812718 and rs2298771) gene polymorphisms were previously indicated to be associated with carbamazepine (CBZ) metabolism and resistance in epilepsy. However, previous studies regarding the effects of these polymorphisms still remain controversial. Therefore, we performed a meta-analysis to evaluate whether the four polymorphisms are associated with CBZ metabolism and resistance.
The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc and Wan Fang Database were searched up to January 2021 for appropriate studies regarding the association of rs2242480, rs776746, rs3812718 and rs2234922 polymorphisms with CBZ metabolism and resistance. The meta-analysis was conducted by Review Manager 5.3 software.
Eighteen studies involving 2546 related epilepsy patients were included. We found that the G allele of CYP3A4 rs2242480 markedly decreased the plasma CBZ concentration in epilepsy. For CYP3A5 rs776746 polymorphism, the GG genotype (homozygote codominant model: GG vs. AA) and GG + GA genotype (dominant model: GG + GA vs. AA and recessive model: GG vs. GA + AA) were respectively found to be significantly associated with increased CBZ plasma concentration. Additionally, it was also found that the SCN1A rs3812718 A allele was significantly associated with decreased CBZ plasma concentration and increased CBZ resistance. However, no association was observed between SCN1A rs2298771 polymorphism and CBZ metabolism and resistance.
The CYP3A4 rs2242480, CYP3A5 rs776746 and SCN1A rs3812718 polymorphisms may play important roles in CBZ metabolism and resistance, while SCN1A rs2298771 polymorphism is not associated with CBZ in epilepsy. These findings would improve the individualized therapy of epileptic patients in clinics.
先前研究表明，细胞色素P450 3A4（CYP3A4，rs2242480）、细胞色素P450 3A5（CYP3A5，rs776746）和电压门控钠通道α亚基1（SCN1A，rs3812718和rs2298771）基因多态性与癫痫患者中卡马西平（CBZ）的代谢及耐药性相关。然而，先前关于这些多态性影响的研究仍存在争议。因此，我们进行了一项荟萃分析，以评估这四种多态性是否与CBZ代谢及耐药性相关。
检索了截至2021年1月的PubMed、EMBASE、Cochrane图书馆、中国知网、维普中文科技期刊数据库、中国生物医学文献数据库和万方数据库，以查找关于rs2242480、rs776746、rs3812718和rs2234922多态性与CBZ代谢及耐药性关联的相关研究。采用Review Manager 5.3软件进行荟萃分析。
纳入了18项研究，涉及2546例相关癫痫患者。我们发现，CYP3A4 rs2242480的G等位基因显著降低了癫痫患者血浆中CBZ的浓度。对于CYP3A5 rs776746多态性，分别发现GG基因型（共显性模型：GG与AA）和GG + GA基因型（显性模型：GG + GA与AA，隐性模型：GG与GA + AA）与CBZ血浆浓度升高显著相关。此外，还发现SCN1A rs3812718的A等位基因与CBZ血浆浓度降低及CBZ耐药性增加显著相关。然而，未观察到SCN1A rs2298771多态性与CBZ代谢及耐药性之间存在关联。
CYP3A4 rs2242480、CYP3A5 rs776746和SCN1A rs3812718多态性可能在CBZ代谢及耐药性中起重要作用，而SCN1A rs2298771多态性与癫痫患者中的CBZ无关。这些发现将有助于改善临床中癫痫患者的个体化治疗。
