Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response.
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.
Ji
Y
Y
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Biernacka
J
J
Snyder
K
K
Drews
M
M
Pelleymounter
L L
LL
Colby
C
C
Wang
L
L
Mrazek
D A
DA
Weinshilboum
R M
RM
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
D002394:Catechol O-Methyltransferase; D017367:Selective Serotonin Reuptake Inhibitors