ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment

Keh Ming Lin, Yen Feng Chiu, I. Ju Tsai, Chia Hui Chen, Winston W. Shen, Shu Chih Liu, Shao Chun Lu, Chia Yih Liu, Mei Chun Hsiao, Hwa Sheng Tang, Shen Ing Liu, Liang Huey Chang, Chi Shin Wu, Hsiao Hui Tsou, Ming Hsien Tsai, Chun Yu Chen, Su Mei Wang, Hsiang Wei Kuo, Ya Ting Hsu, Yu Li Liu

Research output: Contribution to journalArticle

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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. Conclusion 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. Pharmacogenetics and Genomics 21:163-170.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
JournalPharmacogenetics and Genomics
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 2011

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Citalopram
Major Depressive Disorder
Depression
Haplotypes
Genes
Blood-Brain Barrier
Introns
Single Nucleotide Polymorphism
Anxiety
Central Nervous System Agents
Therapeutics
Pharmacogenetics
Genetic Polymorphisms
Genomics
Pharmaceutical Preparations
Antidepressive Agents
Intestines
Endothelial Cells
Adenosine Triphosphate
Epithelial Cells

Keywords

  • ABCB1
  • Escitalopram
  • Hamilton rating scale for depression
  • Major depressive disorder
  • Multidrug resistance 1
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. / Lin, Keh Ming; Chiu, Yen Feng; Tsai, I. Ju; Chen, Chia Hui; Shen, Winston W.; Liu, Shu Chih; Lu, Shao Chun; Liu, Chia Yih; Hsiao, Mei Chun; Tang, Hwa Sheng; Liu, Shen Ing; Chang, Liang Huey; Wu, Chi Shin; Tsou, Hsiao Hui; Tsai, Ming Hsien; Chen, Chun Yu; Wang, Su Mei; Kuo, Hsiang Wei; Hsu, Ya Ting; Liu, Yu Li.

In: Pharmacogenetics and Genomics, Vol. 21, No. 4, 04.2011, p. 163-170.

Research output: Contribution to journalArticle

Lin, KM, Chiu, YF, Tsai, IJ, Chen, CH, Shen, WW, Liu, SC, Lu, SC, Liu, CY, Hsiao, MC, Tang, HS, Liu, SI, Chang, LH, Wu, CS, Tsou, HH, Tsai, MH, Chen, CY, Wang, SM, Kuo, HW, Hsu, YT & Liu, YL 2011, 'ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment', Pharmacogenetics and Genomics, vol. 21, no. 4, pp. 163-170. https://doi.org/10.1097/FPC.0b013e32833db216
Lin, Keh Ming ; Chiu, Yen Feng ; Tsai, I. Ju ; Chen, Chia Hui ; Shen, Winston W. ; Liu, Shu Chih ; Lu, Shao Chun ; Liu, Chia Yih ; Hsiao, Mei Chun ; Tang, Hwa Sheng ; Liu, Shen Ing ; Chang, Liang Huey ; Wu, Chi Shin ; Tsou, Hsiao Hui ; Tsai, Ming Hsien ; Chen, Chun Yu ; Wang, Su Mei ; Kuo, Hsiang Wei ; Hsu, Ya Ting ; Liu, Yu Li. / ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. In: Pharmacogenetics and Genomics. 2011 ; Vol. 21, No. 4. pp. 163-170.
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T1 - ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment

AU - Lin, Keh Ming

AU - Chiu, Yen Feng

AU - Tsai, I. Ju

AU - Chen, Chia Hui

AU - Shen, Winston W.

AU - Liu, Shu Chih

AU - Lu, Shao Chun

AU - Liu, Chia Yih

AU - Hsiao, Mei Chun

AU - Tang, Hwa Sheng

AU - Liu, Shen Ing

AU - Chang, Liang Huey

AU - Wu, Chi Shin

AU - Tsou, Hsiao Hui

AU - Tsai, Ming Hsien

AU - Chen, Chun Yu

AU - Wang, Su Mei

AU - Kuo, Hsiang Wei

AU - Hsu, Ya Ting

AU - Liu, Yu Li

PY - 2011/4

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N2 - 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. Conclusion 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. Pharmacogenetics and Genomics 21:163-170.

AB - 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. Conclusion 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. Pharmacogenetics and Genomics 21:163-170.

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KW - Major depressive disorder

KW - Multidrug resistance 1

KW - Single nucleotide polymorphism

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