CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine

Keh Ming Lin, Hsiao Hui Tsou, I. Ju Tsai, Mei Chun Hsiao, Chin Fu Hsiao, Chia Yih Liu, Winston W. Shen, Hwa Sheng Tang, Chun Kai Fang, Chi Shin Wu, Shao Chun Lu, Hsiang Wei Kuo, Shu Chih Liu, Hsiu Wen Chan, Ya Ting Hsu, Jia Ni Tian, Yu Li Liu

Research output: Contribution to journalArticle

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Abstract

Aim: Paroxetine is a drug of choice in the treatment of major depressive disorder (MDD). Its metabolism has recently been reported to be mediated through the CYP enzymes 1A2 and 2D6. In our current study, we tested whether genetic polymorphisms in CYP1A2 are associated with the treatment efficacy and side effects of paroxetine. Materials & methods: A total of 241 MDD patients who had taken paroxetine continually for 8 weeks were recruited, and their steady state paroxetine concentrations were measured at weeks 2, 4 and 8. The genotypes of these patients were then assessed for the presence of nine SNPs, which were selected from either the HapMap Chinese ethnic group, the literature report or through their functional role in the CYP1A2 gene. Results: The allele types for SNPs rs4646425 (permutation p = 0.03), rs2472304 (permutation p = 0.01) and rs2470890 (permutation p = 0.004) demonstrated significant associations with paroxetine treatment remission at week 8. Response rates in the Hamilton Rating Scale for Depression (HAM-D) and for The Hamilton Rating Scale for Anxiety (HAM-A) were significantly associated with the SNPs rs4646425 (p = 0.0126 and 0.0088 for HAM-D and HAM-A, respectively) and rs4646427 (p = 0.0067 and 0.0196 for HAM-D and HAM-A, respectively). The inducible SNP rs762551 had a significant association with paroxetine dose at week 4 (permutation p = 0.012). We did not find an association between these SNPs and the side effects or serum concentrations of paroxetine. Conclusion: Genetic variants in the CYP1A2 region may be indicators of treatment response in MDD patients to paroxetine.

Original languageEnglish
Pages (from-to)1535-1543
Number of pages9
JournalPharmacogenomics
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Cytochrome P-450 CYP1A2
Paroxetine
Genetic Polymorphisms
Antidepressive Agents
Single Nucleotide Polymorphism
Major Depressive Disorder
Therapeutics
HapMap Project
Cytochrome P-450 CYP2D6
Ethnic Groups
Anxiety
Alleles
Genotype
Depression
Enzymes

Keywords

  • CYP1A2
  • depression
  • HAM-A n HAM-D
  • paroxetine
  • SNP

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine

Cite this

Lin, K. M., Tsou, H. H., Tsai, I. J., Hsiao, M. C., Hsiao, C. F., Liu, C. Y., ... Liu, Y. L. (2010). CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine. Pharmacogenomics, 11(11), 1535-1543. https://doi.org/10.2217/pgs.10.128

CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine. / Lin, Keh Ming; Tsou, Hsiao Hui; Tsai, I. Ju; Hsiao, Mei Chun; Hsiao, Chin Fu; Liu, Chia Yih; Shen, Winston W.; Tang, Hwa Sheng; Fang, Chun Kai; Wu, Chi Shin; Lu, Shao Chun; Kuo, Hsiang Wei; Liu, Shu Chih; Chan, Hsiu Wen; Hsu, Ya Ting; Tian, Jia Ni; Liu, Yu Li.

In: Pharmacogenomics, Vol. 11, No. 11, 11.2010, p. 1535-1543.

Research output: Contribution to journalArticle

Lin, KM, Tsou, HH, Tsai, IJ, Hsiao, MC, Hsiao, CF, Liu, CY, Shen, WW, Tang, HS, Fang, CK, Wu, CS, Lu, SC, Kuo, HW, Liu, SC, Chan, HW, Hsu, YT, Tian, JN & Liu, YL 2010, 'CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine', Pharmacogenomics, vol. 11, no. 11, pp. 1535-1543. https://doi.org/10.2217/pgs.10.128
Lin, Keh Ming ; Tsou, Hsiao Hui ; Tsai, I. Ju ; Hsiao, Mei Chun ; Hsiao, Chin Fu ; Liu, Chia Yih ; Shen, Winston W. ; Tang, Hwa Sheng ; Fang, Chun Kai ; Wu, Chi Shin ; Lu, Shao Chun ; Kuo, Hsiang Wei ; Liu, Shu Chih ; Chan, Hsiu Wen ; Hsu, Ya Ting ; Tian, Jia Ni ; Liu, Yu Li. / CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine. In: Pharmacogenomics. 2010 ; Vol. 11, No. 11. pp. 1535-1543.
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AU - Tsou, Hsiao Hui

AU - Tsai, I. Ju

AU - Hsiao, Mei Chun

AU - Hsiao, Chin Fu

AU - Liu, Chia Yih

AU - Shen, Winston W.

AU - Tang, Hwa Sheng

AU - Fang, Chun Kai

AU - Wu, Chi Shin

AU - Lu, Shao Chun

AU - Kuo, Hsiang Wei

AU - Liu, Shu Chih

AU - Chan, Hsiu Wen

AU - Hsu, Ya Ting

AU - Tian, Jia Ni

AU - Liu, Yu Li

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