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Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response

The Pharmacogenomics Journal volume 12, pages 78–85 (2012)Cite this article

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Abstract

We applied a systematic pharmacogenetic approach to investigate the role of genetic variation in the gene encoding catechol O-methyltransferase (COMT) in individual variation in selective serotonin reuptake inhibitor (SSRI) response among depressed patients. In all, 23 single-nucleotide polymorphisms (SNPs) in COMT were genotyped using DNA from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (N=1914). One SNP, rs13306278, located in the distal promoter region of COMT, showed significant association with remission in White non-Hispanic (WNH) subjects (P=0.038). Electromobility shift assay for rs13306278 showed alternation in the ability of the variant sequence to bind nuclear proteins. A replication study was performed using samples from the Mayo Clinic Pharmacogenetics Research Network Citalopram/Escitalopram Pharmacogenomic study (N=422) that demonstrated a similar trend for association. Our findings suggest that novel genetic markers in the COMT distal promoter may influence SSRI response phenotypes.

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Acknowledgements

This research was supported, in part, by NIH grants RO1 GM28157, U01 GM61388 (The Pharmacogenomics Research Network) and P20 AA17830 as well as a PhRMA Foundation Center of Excellence in Clinical Pharmacology Award. (ClinicalTrials.gov number NCT00613470) We thank Luanne Wussow for her assistance with the preparation of the paper.

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Author notes

  1. Y Ji and J Biernacka: These two authors contributed equally to this work.

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, MN, USA

    Y Ji, L L Pelleymounter, L Wang & R M Weinshilboum

  2. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

    J Biernacka, K Snyder, M Drews & D A Mrazek

  3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    J Biernacka & C Colby

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Correspondence to R M Weinshilboum.

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Ji, Y., Biernacka, J., Snyder, K. et al. Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response. Pharmacogenomics J 12, 78–85 (2012). https://doi.org/10.1038/tpj.2010.69

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