ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment.
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.
Lin
Keh-Ming
KM
Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Chiu
Yen-Feng
YF
Tsai
I-Ju
IJ
Chen
Chia-Hui
CH
Shen
Winston W
WW
Liu
Shu Chih
SC
Lu
Shao-Chun
SC
Liu
Chia-Yih
CY
Hsiao
Mei-Chun
MC
Tang
Hwa-Sheng
HS
Liu
Shen-Ing
SI
Chang
Liang-Huey
LH
Wu
Chi-Shin
CS
Tsou
Hsiao-Hui
HH
Tsai
Ming-Hsien
MH
Chen
Chun-Yu
CY
Wang
Su-Mei
SM
Kuo
Hsiang-Wei
HW
Hsu
Ya-Ting
YT
Liu
Yu-Li
YL
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
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