title: ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment.
abstract: OBJECTIVE
  ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) is a drug transporter protein expressed on the epithelial cells of the intestine and the endothelial cells of the blood-brain barrier. Intestinal ABCB1 actively transports drugs from the cell membrane and prevents them from entering the blood stream whereas the blood-brain barrier ABCB1 prevents drugs from entering the central nervous system. In this study, we tested whether genetic polymorphisms within the ABCB1 gene are associated with the severity of depression and the effectiveness of the antidepressant, escitalopram (S-CIT), in treating major depressive disorder (MDD).
  
  
  METHODS
  Twenty single nucleotide polymorphisms in the ABCB1 gene were selected and genotyped in 100 MDD patients who had undergone S-CIT treatment continuously for 8 weeks. The serum concentrations of S-CIT and its metabolites (S-desmethylcitalopram and S-didesmethylcitalopram) were then measured at weeks 2, 4, and 8.
  
  
  RESULTS
  The ABCB1 genotypes of rs1922242 (P=0.0028) and rs1202184 (P=0.0021) showed significant association with the severity of depressive symptoms as assessed by the Hamilton Rating Scale for Depression adjusted with Hamilton Rating Scale for Anxiety. The haplotype block, rs1882478-rs2235048-rs2235047-rs1045642-rs6949448 (from intron 27 to intron 26), of ABCB1 was found strongly associated with the remission rate (global P=0.003, d.f.=69) in which haplotype T-T-T-C-C was associated with a slower remission rate on S-CIT treatment (P=0.001). The haplotypes may not be indicators of the severity of depression or anxiety.
  
  
  CONCLUSIONS
  Our findings suggest that single nucleotide polymorphisms in the ABCB1 gene may be indicators of the severity of depression and of the likely S-CIT treatment remission response in MDD.
authors.affiliation: Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Keh-Ming
authors.initials: KM
authors.lastname: Lin
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Tsai
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chen
authors.forename: Winston W
authors.initials: WW
authors.lastname: Shen
authors.forename: Shu Chih
authors.initials: SC
authors.lastname: Liu
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Lu
authors.forename: Chia-Yih
authors.initials: CY
authors.lastname: Liu
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Hsiao
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: Chi-Shin
authors.initials: CS
authors.lastname: Wu
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Tsou
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Tsai
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Su-Mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Hsiang-Wei
authors.initials: HW
authors.lastname: Kuo
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Hsu
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D015283:Citalopram / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram