title: CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions.
abstract: OBJECTIVE
  The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT.
  
  
  METHODS
  Ten SNPs in CYP1A2 were selected and genotyped in 158 patients under S-CIT treatment. The serum levels of S-CIT and its metabolites were measured by HPLC.
  
  
  RESULTS
  CYP1A2 SNPs rs2069521, rs2069526, rs4646425 and rs4646427 are significantly associated with the metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004, respectively) at week 2 of treatment. Carriers of the allele types associated with higher S-DDCIT/S-DCIT ratios had more severe side effects.
  
  
  CONCLUSIONS
  These results suggest that genetic variants in CYP1A2 may be indicators for S-CIT metabolism and that the fast metabolizers may experience more severe adverse reactions in the early stages of S-CIT treatment. Original submitted 27 December 2012; Revision submitted 15 May 2013.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Kuo
authors.forename: Shu Chih
authors.initials: SC
authors.lastname: Liu
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Liu
authors.forename: Keh-Ming
authors.initials: KM
authors.lastname: Lin
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Lu
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Hsiao
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
authors.forename: Chia-Yih
authors.initials: CY
authors.lastname: Liu
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chen
authors.forename: Mong-Liang
authors.initials: ML
authors.lastname: Lu
authors.forename: Winston W
authors.initials: WW
authors.lastname: Shen
authors.forename: Hwa-Sheng
authors.initials: HS
authors.lastname: Tang
authors.forename: Shen-Ing
authors.initials: SI
authors.lastname: Liu
authors.forename: Liang-Huey
authors.initials: LH
authors.lastname: Chang
authors.forename: Hsiao-Yu
authors.initials: HY
authors.lastname: Wu
authors.forename: Yao-Sheng
authors.initials: YS
authors.lastname: Chang
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Andrew Ch
authors.initials: ACh
authors.lastname: Chen
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D019388:Cytochrome P-450 CYP1A2