ArticlePharmacogenomics and personalized medicine2014
Effects of EPHX1 and CYP3A4 polymorphisms on carbamazepine metabolism in epileptic patients.
Article in Pharmacogenomics and personalized medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Pharmacogenetics of Carbamazepine: A Systematic Review on CYP3A4 and CYP3A5 Polymorphisms.CNS & neurological disorders drug targets · 2024Pooled it
- Natural Polymorphic Variants in the CYP450 Superfamily: A Review of Potential Structural Mechanisms and Functional Consequences.International journal of molecular sciences · 2025Review
- Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential.Geriatrics (Basel, Switzerland) · 2023Article
- Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine.British journal of clinical pharmacology · 2021Article
- Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Vitamin D and Genetic Susceptibility to Multiple Sclerosis.Biochemical genetics · 2021Review
- Whole-Exome Sequencing in Patients Affected by Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Reveals New Variants Potentially Contributing to the Phenotype.Pharmacogenomics and personalized medicine · 2021Article
- How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?Frontiers in genetics · 2020Review
- Mutant GNLY is linked to Stevens-Johnson syndrome and toxic epidermal necrolysis.Human genetics · 2019Article
- Non-Skeletal Activities of Vitamin D: From Physiology to Brain Pathology.Medicina (Kaunas, Lithuania) · 2019Review
- Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese population.BMC neurology · 2019Article
- Effects ofFrontiers in public health · 2019Article
- CYP27A1, CYP24A1, and RXR-α Polymorphisms, Vitamin D, and Multiple Sclerosis: a Pilot Study.Journal of molecular neuroscience : MN · 2018Article
- The immunological implication of the new vitamin D metabolism.Central-European journal of immunology · 2018Review
- Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease.Gene · 2015Review
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of this study was to investigate the effect of two genetic polymorphisms in the coding regions (exon 3 and exon 4) of the EPHX1 gene, ie, 337T>C and 416A>G, respectively, on the metabolism of carbamazepine (CBZ) 10,11-epoxide (the active metabolite of CBZ) by evaluating the variation in serum CBZ 10,11-epoxide levels 4 hours after administration of the drug. Moreover, we reported the genotype frequencies of the CYP3A4*22 (rs 35599367, C>T) variant and its influence on the metabolism of CBZ.
methodsThe analysis was performed in 50 patients receiving CBZ as monotherapy. DNA was extracted from leukocytes using a commercially available kit. Serum CBZ 10,11-epoxide levels were measured by high-performance liquid chromatography. Allelic discrimination was performed using polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the difference in mean values for CBZ 10,11-epoxide levels according to genotype was performed using the Student's t-test with Statistical Package for the Social Sciences version 13 software.
resultsFourteen percent of the study group were CC, 42% were CT, and 44% were TT for the EPHX1 337T>C variant. No GG homozygote was identified for the EPHX1 416A>G variant; 64% were AA and 36% were AG. When we compared serum CBZ 10,11-epoxide levels 4 hours after drug administration, we found no statistically significant difference between the 337 CC, CT, and TT genotypes. Similarly, no difference in serum CBZ 10,11-epoxide levels was found between 416A>G AA and AG. Genotype frequencies for the CYP3A4*22 (rs 35599367 C>T) allelic variant were 94% for CC and 6% for CT, with no statistically significant difference in serum CBZ 10,11-epoxide levels between these genotypes 4 hours after administration of the drug (2.6±1.3 μg/μL and 2.5±1.2 μg/μL, respectively).
conclusionAlthough there is some evidence of involvement of these polymorphisms in enzyme activity in vitro, we found no interference with CBZ metabolism in vivo.
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