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 (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.
authors.affiliation: Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.forename: J
authors.initials: J
authors.lastname: Biernacka
authors.forename: K
authors.initials: K
authors.lastname: Snyder
authors.forename: M
authors.initials: M
authors.lastname: Drews
authors.forename: L L
authors.initials: LL
authors.lastname: Pelleymounter
authors.forename: C
authors.initials: C
authors.lastname: Colby
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: D A
authors.initials: DA
authors.lastname: Mrazek
authors.forename: R M
authors.initials: RM
authors.lastname: Weinshilboum
mesh_terms: D002394:Catechol O-Methyltransferase / Q000235:genetics*; D045744:Cell Line, Tumor; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002394:Catechol O-Methyltransferase; D017367:Selective Serotonin Reuptake Inhibitors