CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions

Hsiang Wei Kuo, Shu Chih Liu, Hsiao Hui Tsou, Sheng Wen Liu, Keh Ming Lin, Shao Chun Lu, Mei Chun Hsiao, Chin Fu Hsiao, Chia Yih Liu, Chia Hui Chen, Mong Liang Lu, Winston W. Shen, Hwa Sheng Tang, Shen Ing Liu, Liang Huey Chang, Hsiao Yu Wu, Yao Sheng Chang, Teng Kuang Yeh, Andrew Ch Chen, Yu Li Liu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Aim: 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. Materials & 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. Conclusion: 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 201.

Original languageEnglish
Pages (from-to)1191-1201
Number of pages11
JournalPharmacogenomics
Volume14
Issue number10
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP1A2
Citalopram
Genetic Polymorphisms
Antidepressive Agents
Single Nucleotide Polymorphism
Therapeutics
Alleles
High Pressure Liquid Chromatography
Liver
Enzymes
Serum
Genes
desmethylcitalopram
didesmethylcitalopram

Keywords

  • CYP1A2
  • escitalopram
  • major depressive disorder
  • side effects
  • SNP

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine
  • Medicine(all)

Cite this

Kuo, H. W., Liu, S. C., Tsou, H. H., Liu, S. W., Lin, K. M., Lu, S. C., ... Liu, Y. L. (2013). CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions. Pharmacogenomics, 14(10), 1191-1201. https://doi.org/10.2217/pgs.13.105

CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions. / Kuo, Hsiang Wei; Liu, Shu Chih; Tsou, Hsiao Hui; Liu, Sheng Wen; Lin, Keh Ming; Lu, Shao Chun; Hsiao, Mei Chun; Hsiao, Chin Fu; Liu, Chia Yih; Chen, Chia Hui; Lu, Mong Liang; Shen, Winston W.; Tang, Hwa Sheng; Liu, Shen Ing; Chang, Liang Huey; Wu, Hsiao Yu; Chang, Yao Sheng; Yeh, Teng Kuang; Chen, Andrew Ch; Liu, Yu Li.

In: Pharmacogenomics, Vol. 14, No. 10, 2013, p. 1191-1201.

Research output: Contribution to journalArticle

Kuo, HW, Liu, SC, Tsou, HH, Liu, SW, Lin, KM, Lu, SC, Hsiao, MC, Hsiao, CF, Liu, CY, Chen, CH, Lu, ML, Shen, WW, Tang, HS, Liu, SI, Chang, LH, Wu, HY, Chang, YS, Yeh, TK, Chen, AC & Liu, YL 2013, 'CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions', Pharmacogenomics, vol. 14, no. 10, pp. 1191-1201. https://doi.org/10.2217/pgs.13.105
Kuo, Hsiang Wei ; Liu, Shu Chih ; Tsou, Hsiao Hui ; Liu, Sheng Wen ; Lin, Keh Ming ; Lu, Shao Chun ; Hsiao, Mei Chun ; Hsiao, Chin Fu ; Liu, Chia Yih ; Chen, Chia Hui ; Lu, Mong Liang ; Shen, Winston W. ; Tang, Hwa Sheng ; Liu, Shen Ing ; Chang, Liang Huey ; Wu, Hsiao Yu ; Chang, Yao Sheng ; Yeh, Teng Kuang ; Chen, Andrew Ch ; Liu, Yu Li. / CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions. In: Pharmacogenomics. 2013 ; Vol. 14, No. 10. pp. 1191-1201.
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abstract = "Aim: 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. Materials & 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. Conclusion: 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 201.",
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T1 - CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions

AU - Kuo, Hsiang Wei

AU - Liu, Shu Chih

AU - Tsou, Hsiao Hui

AU - Liu, Sheng Wen

AU - Lin, Keh Ming

AU - Lu, Shao Chun

AU - Hsiao, Mei Chun

AU - Hsiao, Chin Fu

AU - Liu, Chia Yih

AU - Chen, Chia Hui

AU - Lu, Mong Liang

AU - Shen, Winston W.

AU - Tang, Hwa Sheng

AU - Liu, Shen Ing

AU - Chang, Liang Huey

AU - Wu, Hsiao Yu

AU - Chang, Yao Sheng

AU - Yeh, Teng Kuang

AU - Chen, Andrew Ch

AU - Liu, Yu Li

PY - 2013

Y1 - 2013

N2 - Aim: 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. Materials & 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. Conclusion: 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 201.

AB - Aim: 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. Materials & 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. Conclusion: 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 201.

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KW - major depressive disorder

KW - side effects

KW - SNP

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