Shravan Venkatraman, Kesavan Ramasamy, Pradeep P Nair, Priyadharsini Rajendran
{"title":"EPHX1 c.337的影响T>C和UGT2B7*2基因多态性对印度南部癫痫患者卡马西平维持剂量需求的横断面遗传关联研究","authors":"Shravan Venkatraman, Kesavan Ramasamy, Pradeep P Nair, Priyadharsini Rajendran","doi":"10.1515/dmpt-2022-0157","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having a role in the requirement of CBZ maintenance dose. The aim was to study the influence of <i>EPHX1</i> c.337 T>C and <i>UGT2B7*2</i> genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy.</p><p><strong>Methods: </strong>Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10% EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of <i>EPHX1</i> c.337 T>C and <i>UGT2B7*2</i>, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between the genotypes and CBZ maintenance dose requirement for dominant and recessive models of <i>EPHX1 c.337 T>C</i> and <i>UGT2B7*2</i>. A value of p<0.05 was considered to be statistically significant.</p><p><strong>Results: </strong>For <i>UGT2B7*2</i> (rs 7439366), CT required a higher dose (CT 626 mg/day and TT 523 mg/day) but not found to be significant (p-value 0.167). PWE carrying CT genotype of <i>EPHX1</i> c.337 T>C had 62 mg higher dose when compared to homozygous mutant CC (590 mg/day for CT and 528 mg/day for CC) but p-value was not found to be significant (p-value 0.835).</p><p><strong>Conclusions: </strong>The results of our study done in 115 PWE showed there was a lack of association between SNPs of <i>EPHX1</i> c.337 T>C, <i>UGT2B7*2</i> and CBZ maintenance dose requirement in Southern part of India and this finding has to be confirmed in a larger sample size.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 2","pages":"191-197"},"PeriodicalIF":0.0000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Influence of <i>EPHX1</i> c.337 T>C and <i>UGT2B7*2</i> genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study.\",\"authors\":\"Shravan Venkatraman, Kesavan Ramasamy, Pradeep P Nair, Priyadharsini Rajendran\",\"doi\":\"10.1515/dmpt-2022-0157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having a role in the requirement of CBZ maintenance dose. The aim was to study the influence of <i>EPHX1</i> c.337 T>C and <i>UGT2B7*2</i> genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy.</p><p><strong>Methods: </strong>Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10% EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of <i>EPHX1</i> c.337 T>C and <i>UGT2B7*2</i>, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between the genotypes and CBZ maintenance dose requirement for dominant and recessive models of <i>EPHX1 c.337 T>C</i> and <i>UGT2B7*2</i>. A value of p<0.05 was considered to be statistically significant.</p><p><strong>Results: </strong>For <i>UGT2B7*2</i> (rs 7439366), CT required a higher dose (CT 626 mg/day and TT 523 mg/day) but not found to be significant (p-value 0.167). PWE carrying CT genotype of <i>EPHX1</i> c.337 T>C had 62 mg higher dose when compared to homozygous mutant CC (590 mg/day for CT and 528 mg/day for CC) but p-value was not found to be significant (p-value 0.835).</p><p><strong>Conclusions: </strong>The results of our study done in 115 PWE showed there was a lack of association between SNPs of <i>EPHX1</i> c.337 T>C, <i>UGT2B7*2</i> and CBZ maintenance dose requirement in Southern part of India and this finding has to be confirmed in a larger sample size.</p>\",\"PeriodicalId\":11332,\"journal\":{\"name\":\"Drug metabolism and personalized therapy\",\"volume\":\"38 2\",\"pages\":\"191-197\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug metabolism and personalized therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/dmpt-2022-0157\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug metabolism and personalized therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/dmpt-2022-0157","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study.
Objectives: Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having a role in the requirement of CBZ maintenance dose. The aim was to study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy.
Methods: Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10% EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of EPHX1 c.337 T>C and UGT2B7*2, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between the genotypes and CBZ maintenance dose requirement for dominant and recessive models of EPHX1 c.337 T>C and UGT2B7*2. A value of p<0.05 was considered to be statistically significant.
Results: For UGT2B7*2 (rs 7439366), CT required a higher dose (CT 626 mg/day and TT 523 mg/day) but not found to be significant (p-value 0.167). PWE carrying CT genotype of EPHX1 c.337 T>C had 62 mg higher dose when compared to homozygous mutant CC (590 mg/day for CT and 528 mg/day for CC) but p-value was not found to be significant (p-value 0.835).
Conclusions: The results of our study done in 115 PWE showed there was a lack of association between SNPs of EPHX1 c.337 T>C, UGT2B7*2 and CBZ maintenance dose requirement in Southern part of India and this finding has to be confirmed in a larger sample size.
期刊介绍：
Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.
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