Variation in the genes encoding vesicular monoamine transporter 2 and beta-1 adrenergic receptor and antidepressant treatment outcome.
The identification of genetic variants regulating antidepressant response would allow for more individualized, rational, and successful drug treatments. We previously identified a region of mouse chromosome 19 that strongly influences citalopram response in an antidepressant model, the tail suspension test. By virtue of their location in this loci, expression in brain, and involvement in monoamine neurotransmission, we nominated SLC18A2 (encoding vesicular monoamine transporter 2, a.k.a. VMAT2) and ADRB1 (encoding beta-1 adrenergic receptor) as candidate genes for a human pharmacogenetic study. This study tested for an association between SLC18A2 and ADRB1 and treatment outcome in 873 major depressive disorder patients treated with the antidepressant citalopram in the Sequenced Treatment Alternatives to Relieve Depression study. Haplotype-tagging single nucleotide polymorphisms (four in SLC18A2 and two in ADRB1) were chosen to detect the common genetic variation. We failed to detect any significant association between treatment outcome and genotypes or allele frequencies at any of the markers studied. We did, however, detect ethnic differences in the allele frequencies of five out of six markers. These data do not rule out the possible involvement of SLC18A2 or ADRB1 in antidepressant treatment response as these genes may contribute a small effect size or interact epistatically with other genes.
Crowley
James J
JJ
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Lipsky
Robert H
RH
Lucki
Irwin
I
Berrettini
Wade H
WH
D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D016896:Treatment Outcome; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics*
D000928:Antidepressive Agents; D018342:Receptors, Adrenergic, beta-1; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins