Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response

Y. Ji; J. Biernacka; K. Snyder; M. Drews; L. L. Pelleymounter; C. Colby; L. Wang; D. A. Mrazek; R. M. Weinshilboum

doi:10.1038/tpj.2010.69

Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response

Y. Ji, J. Biernacka, K. Snyder, M. Drews, L. L. Pelleymounter, C. Colby, L. Wang, D. A. Mrazek, R. M. Weinshilboum

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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 (N1914). One SNP, rs13306278, located in the distal promoter region of COMT, showed significant association with remission in White non-Hispanic (WNH) subjects (P0.038). 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 (N422) that demonstrated a similar trend for association. Our findings suggest that novel genetic markers in the COMT distal promoter may influence SSRI response phenotypes.

Original language	English (US)
Pages (from-to)	78-85
Number of pages	8
Journal	Pharmacogenomics Journal
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/tpj.2010.69
State	Published - Feb 2012

Keywords

COMT
STAR*D
catechol O-methyltransferase
major depressive disorder
pharmacogenetics
selective serotonin reuptake inhibitor

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.1038/tpj.2010.69

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title = "Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response",

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 (N1914). One SNP, rs13306278, located in the distal promoter region of COMT, showed significant association with remission in White non-Hispanic (WNH) subjects (P0.038). 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 (N422) that demonstrated a similar trend for association. Our findings suggest that novel genetic markers in the COMT distal promoter may influence SSRI response phenotypes.",

keywords = "COMT, STAR*D, catechol O-methyltransferase, major depressive disorder, pharmacogenetics, selective serotonin reuptake inhibitor",

author = "Y. Ji and J. Biernacka and K. Snyder and M. Drews and Pelleymounter, {L. L.} and C. Colby and L. Wang and Mrazek, {D. A.} and Weinshilboum, {R. M.}",

note = "Funding Information: 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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AU - Drews, M.

AU - Pelleymounter, L. L.

AU - Colby, C.

AU - Wang, L.

AU - Mrazek, D. A.

AU - Weinshilboum, R. M.

N1 - Funding Information: 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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N2 - 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 (N1914). One SNP, rs13306278, located in the distal promoter region of COMT, showed significant association with remission in White non-Hispanic (WNH) subjects (P0.038). 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 (N422) 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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Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response

Abstract

Keywords

ASJC Scopus subject areas

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