印度南部癫痫患者细胞色素 P450 表氧化酶和 UDP-葡糖醛酸基转移酶（UGT）的遗传多态性及其对卡马西平血浆水平和代谢比值的影响：一项横断面遗传关联研究。
Genetic polymorphisms of microsomal epoxide hydrolase and UDP-glucuronosyltransferase (UGT) and its effects on plasma carbamazepine levels and metabolic ratio in persons with epilepsy of South India: A cross-sectional genetic association study.
机构信息
Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
出版信息
Indian J Pharmacol. 2023 May-Jun;55(3):149-154. doi: 10.4103/ijp.ijp_228_22.
OBJECTIVES
Carbamazepine (CBZ), an anti-seizure drug, is widely prescribed for the management of focal seizures. At a given therapeutic dose, CBZ exhibits marked interindividual variation in the plasma CBZ levels. The aim wasto study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on plasma carbamazepine (CBZ) levels in persons with epilepsy (PWE) from South India.
METHODS
115 PWE belong to South India origin who are on carbamazepine monotherapy were recruited. Genotyping of the two variants weredone using RT-PCR method. PWE who had seizure freedom for one year and their last dose which was not changed for one year duration were included and their plasma levels of CBZ and its active metabolite CBZ 10,11 epoxide were analysed by reverse phase HPLC.
RESULTS
In EPHX1 c. 337 (T>C) polymorphism, the PWE carrying CC had lower plasma CBZ levels when compared to CT genotype (2.45 μg/ml vs 3.15 μg/ml. In UGT2B72, PWE carrying homozygous mutant TT had higher levels when compared with CT (3.09 μg/ml vs 2.74 μg/ml) genotype but found no statistical significance. Mutant genotype of EPHX1 (CC) had higher metabolic ratio compared to TT genotype (1.33 vs 1.17) but not found to be statistically significant. Mutant genotype of UGT2B72 (TT) was found to be having lower metabolic ratio when compared with CC genotype (1.18 vs 1.35; p value =0.08).
CONCLUSION
PWE carrying EPHX1 c.337 T>C (rs1051740) and UGT2B7*2 (rs7439366) genetic polymorphisms did not affect the plasma CBZ levels and metabolic ratio of PWE of South Indian origin. However, this finding should be confirmed in a larger sample size which may help in optimization and personalized CBZ therapy in South Indians.
目的
卡马西平（CBZ）是一种抗癫痫药物，广泛用于局灶性癫痫发作的治疗。在给定的治疗剂量下，CBZ 在血浆 CBZ 水平上表现出明显的个体间差异。本研究旨在探讨印度南部癫痫患者（PWE）EPHX1 c.337 T>C 和 UGT2B7*2 基因多态性对卡马西平（CBZ）血浆水平的影响。
方法
招募了 115 名来自印度南部的接受 CBZ 单药治疗的 PWE。使用 RT-PCR 方法对两种变体进行基因分型。纳入无癫痫发作一年且过去一年未改变最后剂量的 PWE，并通过反相高效液相色谱法分析其 CBZ 和其活性代谢物 CBZ 10,11-环氧的血浆水平。
结果
在 EPHX1 c.337（T>C）多态性中，与 CT 基因型相比，携带 CC 的 PWE 具有更低的血浆 CBZ 水平（2.45μg/ml 比 3.15μg/ml）。在 UGT2B72 中，与 CT 基因型相比，携带纯合突变 TT 的 PWE 具有更高的水平（3.09μg/ml 比 2.74μg/ml），但无统计学意义。与 TT 基因型相比，EPHX1 突变基因型（CC）的代谢比值更高（1.33 比 1.17），但无统计学意义。与 CC 基因型相比，UGT2B72 突变基因型（TT）的代谢比值较低（1.18 比 1.35；p 值=0.08）。
结论
携带 EPHX1 c.337 T>C（rs1051740）和 UGT2B7*2（rs7439366）基因多态性的 PWE 不会影响印度南部 PWE 的血浆 CBZ 水平和代谢比值。然而，这一发现需要在更大的样本量中得到证实，这可能有助于优化和个体化 CBZ 治疗在印度南部人群中的应用。
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