PMID- 33333223
OWN - NLM
STAT- MEDLINE
DCOM- 20210121
LR  - 20211204
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 771
DP  - 2021 Mar 1
TI  - Association of xenobiotic receptor polymorphisms with carbamazepine response in 
      epilepsy patients.
PG  - 145359
LID - S0378-1119(20)31028-3 [pii]
LID - 10.1016/j.gene.2020.145359 [doi]
AB  - PURPOSE: Drug-resistant epilepsy is a problem worldwide. Xenobiotic receptors may 
      play a significant role in the establishment of resistance to antiepileptic 
      agents. Previous studies have confirmed that the metabolism and efficacy of 
      carbamazepine (CBZ) can be influenced by xenobiotic receptors, especially 
      pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl 
      hydrocarbon receptor (AHR). Therefore, this study intends to elucidate the 
      pharmacogenomic associations of polymorphisms of these xenobiotic receptors with 
      the CBZ response in epilepsy patients, and these genetic data may be useful for 
      the treatment of clinical prophylaxis and individualized treatment of intractable 
      epilepsy. METHODS: Adult patients with epilepsy who were on CBZ-based monotherapy 
      and combination therapy (n = 257) were genotyped, and the patients were divided 
      into drug-responsive and drug-resistant groups according to the International 
      League Against Epilepsy criteria. We sought to tag single-nucleotide 
      polymorphisms (SNPs) of PXR, CAR and AHR that principally represent alleles 
      associated with drug resistance risk; in addition, a gene interaction analysis 
      reference panel was constructed for SNP-based imputation. RESULTS: No significant 
      effects of PXR or AHR polymorphisms were observed. However, an interaction 
      between the CAR rs2502815 variant and CBZ response was observed: in CBZ-based 
      monotherapy and combination therapy patients, the GG genotype of the CAR 
      rs2502815 variant (vs. wild-type homozygous) was independently associated with 
      CBZ response after adjusting for variables [odds ratio (OR) = 0.389, 95% 
      confidence interval (CI) 0.203-0.743, p = 0.004]. The results of the haplotype 
      and gene interaction case-control analyses of the CBZ response were negative. Our 
      results provide clinical data regarding the genetic possibilities of drug 
      responses related to CAR variation in epilepsy patients. CONCLUSION: This study 
      is the first to indicate a potentially relevant interaction between the CAR 
      rs2502815 polymorphism and the CBZ response in epilepsy patients.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Kong, Fan-Cheng
AU  - Kong FC
AD  - Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Ma, Chun-Lai
AU  - Ma CL
AD  - Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China. 
      Electronic address: chunlaima@126.com.
FAU - Lang, Li-Qin
AU  - Lang LQ
AD  - Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China. 
      Electronic address: langlq1212@163.com.
FAU - Zhong, Ming-Kang
AU  - Zhong MK
AD  - Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20201215
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (AHR protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Constitutive Androstane Receptor)
RN  - 0 (NR1I2 protein, human)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 33CM23913M (Carbamazepine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Basic Helix-Loop-Helix Transcription Factors/*genetics
MH  - Carbamazepine/*administration & dosage/pharmacology
MH  - Case-Control Studies
MH  - Child
MH  - Constitutive Androstane Receptor
MH  - *Drug Resistance
MH  - Epilepsy/*drug therapy/genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Pharmacogenomic Variants
MH  - Polymorphism, Single Nucleotide
MH  - Precision Medicine
MH  - Pregnane X Receptor/*genetics
MH  - Receptors, Aryl Hydrocarbon/*genetics
MH  - Receptors, Cytoplasmic and Nuclear/*genetics
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor (AHR)
OT  - Carbamazepine (CBZ)
OT  - Constitutive androstane receptor (CAR)
OT  - Drug-resistant epilepsy
OT  - Polymorphisms
OT  - Pregnane X receptor (PXR)
EDAT- 2020/12/18 06:00
MHDA- 2021/01/22 06:00
CRDT- 2020/12/17 20:11
PHST- 2020/08/03 00:00 [received]
PHST- 2020/11/03 00:00 [revised]
PHST- 2020/12/01 00:00 [accepted]
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2021/01/22 06:00 [medline]
PHST- 2020/12/17 20:11 [entrez]
AID - S0378-1119(20)31028-3 [pii]
AID - 10.1016/j.gene.2020.145359 [doi]
PST - ppublish
SO  - Gene. 2021 Mar 1;771:145359. doi: 10.1016/j.gene.2020.145359. Epub 2020 Dec 15.