title: Effects of SCN1A and GABA receptor genetic polymorphisms on carbamazepine tolerability and efficacy in Chinese patients with partial seizures: 2-year longitudinal clinical follow-up.
abstract: OBJECTIVE
  To investigate the tolerability and efficacy of carbamazepine treatment in patients with partial-onset seizures and the association with polymorphisms in the sodium channel α-subunit type 1 (SCN1A), and gamma-aminobutyric acid (GABA) receptor genes among the Chinese Han population.
  
  
  METHODS
  448 patients were genotyped for single nucleotide polymorphisms selected of the SCN1A and GABA-receptor genes. Monotherapy with carbamazepine (CBZ) was administered to the patients. The effectiveness of CBZ treatment was evaluated with regard to efficacy by the decrease in seizures and tolerability by retention rates.
  
  
  RESULTS
  SCN1A rs3812718 A/G with CBZ tolerability (P= 0.038) throughout 24 months of clinical follow-up and the GABRA1 rs2290732 A/G were significantly associated with CBZ tolerability (P= 0.001). The maintenance dose and serum level of CBZ in AA genotype carriers of rs3812718 A/G were significantly higher than those of GG genotype carriers between 3 and 12 months of follow-up. The proportion of AA genotype carriers of rs2298771 A/G with seizure free was significantly higher than that of AG+GG genotype carriers from 3 months to 15 months of follow-up (P < 0.05).
  
  
  CONCLUSIONS
  rs3812718 A/G and rs2290732 A/G polymorphisms affected the tolerability of CBZ. rs2298771 A/G was associated with efficacy of CBZ treatment.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: Bo-Ting
authors.initials: BT
authors.lastname: Zhou
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Zhou
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Xu
authors.forename: Ding
authors.initials: D
authors.lastname: Liu
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics*; D018079:Receptors, GABA / Q000235:genetics*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; D018079:Receptors, GABA; C568242:SCN1A protein, human; D002220:Carbamazepine