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.
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引用次数: 0
Abstract
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 UGT2B7*2, 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 UGT2B7*2 (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，被广泛用于治疗局灶性癫痫。在给定的治疗剂量下，CBZ在血浆CBZ水平上表现出显著的个体间变化。研究EPHX1c.337T>c和UGT2B7*2基因多态性对南印度癫痫患者血浆卡马西平（CBZ）水平的影响。用RT-PCR方法对两种变体进行基因分型。结果：在EPHX1c.337（T>c）多态性中，与CT基因型相比，携带CC的PWE具有较低的血浆CBZ水平（2.45μg/ml vs 3.15μg/ml）。在UGT2B7*2中，携带纯合突变TT的PWE与CT（3.09μg/ml vs 2.74μg/ml）基因型相比具有较高的水平，但没有发现统计学意义。与TT基因型相比，EPHX1（CC）的突变基因型具有更高的代谢率（1.33vs1.17），但没有发现统计学意义。与CC基因型相比，UGT2B7*2（TT）突变基因型的代谢率较低（1.18vs1.35；p值=0.08）。然而，这一发现应该在更大的样本量中得到证实，这可能有助于南印度人的优化和个性化CBZ治疗。
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Indian Journal of Pharmacology accepts, in English, review articles, articles for educational forum, original research articles (full length and short communications), letter to editor, case reports and interesting fillers. Articles concerning all aspects of pharmacology will be considered. Articles of general interest (e.g. methods, therapeutics, medical education, interesting websites, new drug information and commentary on a recent topic) are also welcome.
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