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Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.

Publication ,  Journal Article
Ji, Y; Hebbring, S; Zhu, H; Jenkins, GD; Biernacka, J; Snyder, K; Drews, M; Fiehn, O; Zeng, Z; Schaid, D; Mrazek, DA; Kaddurah-Daouk, R ...
Published in: Clin Pharmacol Ther
January 2011

Major depressive disorder (MDD) is a common psychiatric disease. Selective serotonin reuptake inhibitors (SSRIs) are an important class of drugs used in the treatment of MDD. However, many patients do not respond adequately to SSRI therapy. We used a pharmacometabolomics-informed pharmacogenomic research strategy to identify citalopram/escitalopram treatment outcome biomarkers. Metabolomic assay of plasma samples from 20 escitalopram remitters and 20 nonremitters showed that glycine was negatively associated with treatment outcome (P = 0.0054). This observation was pursued by genotyping tag single-nucleotide polymorphisms (SNPs) for genes encoding glycine synthesis and degradation enzymes, using 529 DNA samples from SSRI-treated MDD patients. The rs10975641 SNP in the glycine dehydrogenase (GLDC) gene was associated with treatment outcome phenotypes. Genotyping for rs10975641 was carried out in 1,245 MDD patients in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, and its presence was significant (P = 0.02) in DNA taken from these patients. These results highlight a possible role for glycine in SSRI response and illustrate the use of pharmacometabolomics to "inform" pharmacogenomics.

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Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

January 2011

Volume

89

Issue

1

Start / End Page

97 / 104

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Nuclear Proteins
  • Metabolome
  • Male
  • Linkage Disequilibrium
  • Introns
  • Humans
  • Glycine Dehydrogenase (Decarboxylating)
 

Citation

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Ji, Y., Hebbring, S., Zhu, H., Jenkins, G. D., Biernacka, J., Snyder, K., … Weinshilboum, R. M. (2011). Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin Pharmacol Ther, 89(1), 97–104. https://doi.org/10.1038/clpt.2010.250
Ji, Y., S. Hebbring, H. Zhu, G. D. Jenkins, J. Biernacka, K. Snyder, M. Drews, et al. “Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.Clin Pharmacol Ther 89, no. 1 (January 2011): 97–104. https://doi.org/10.1038/clpt.2010.250.
Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, Snyder K, et al. Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin Pharmacol Ther. 2011 Jan;89(1):97–104.
Ji, Y., et al. “Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.Clin Pharmacol Ther, vol. 89, no. 1, Jan. 2011, pp. 97–104. Pubmed, doi:10.1038/clpt.2010.250.
Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, Snyder K, Drews M, Fiehn O, Zeng Z, Schaid D, Mrazek DA, Kaddurah-Daouk R, Weinshilboum RM. Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin Pharmacol Ther. 2011 Jan;89(1):97–104.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

January 2011

Volume

89

Issue

1

Start / End Page

97 / 104

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Nuclear Proteins
  • Metabolome
  • Male
  • Linkage Disequilibrium
  • Introns
  • Humans
  • Glycine Dehydrogenase (Decarboxylating)