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.

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.

• Authors: Shravan Venkatraman, Kesavan Ramasamy, Pradeep Pankajakshan Nair
• Journal: Indian journal of pharmacology (Indian J Pharmacol) 2023 May-Jun Vol. 55 Issue 3 Pg. 149-154 ISSN: 1998-3751 [Electronic] India
• PMID: 37555408 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Epoxide Hydrolases
• Glucuronosyltransferase
• Carbamazepine
• Benzodiazepines
• Uridine Diphosphate

Topics

• Humans
• Anticonvulsants
• Epoxide Hydrolases (genetics, therapeutic use)
• Glucuronosyltransferase (genetics, therapeutic use)
• Cross-Sectional Studies
• Polymorphism, Single Nucleotide
• Epilepsy (drug therapy, genetics)
• Carbamazepine
• Benzodiazepines (therapeutic use)
• Genetic Association Studies
• Uridine Diphosphate (therapeutic use)