title: Effects of ABCB1 polymorphisms on plasma carbamazepine concentrations and pharmacoresistance in Chinese patients with epilepsy.
abstract: P-glycoprotein may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCB1 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. C1236T, G2677T/A, and C3435T polymorphisms of ABCB1 were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 84 patients treated with CBZ monotherapy. Patients with 3435-TT (n=15) had lower adjusted CBZ concentrations than those with 3435-CC (n=30) (P=0.026). However there were no associations between all the studied genotypes, haplotypes, or diplotypes involving ABCB1 C1236T, G2677T/A, and C3435T polymorphisms and pharmacoresistance in the patient cohort. Our results suggest that ABCB1 3435-TT is associated with decreased plasma CBZ levels in Chinese patients with epilepsy. However, whether this contributes to CBZ resistance needs to be further investigated in a larger cohort of patients.
authors.affiliation: The First Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Meng
authors.forename: Guimei
authors.initials: G
authors.lastname: Guo
authors.forename: Jinyan
authors.initials: J
authors.lastname: Ren
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ge
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Guo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002220:Carbamazepine / Q000097:blood* / Q000627:therapeutic use*; D015331:Cohort Studies; D004351:Drug Resistance / Q000235:genetics; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D002220:Carbamazepine