Analysis of 34 candidate genes in bupropion and placebo remission

There is considerable variability in the rate of response and remission following treatment with antidepressant drugs or placebo in depression patients. No pharmacogenetic studies of bupropion response have been done. We investigated 532 tagging single nucleotide polymorphisms (SNPs) in 34 candidate genes for association with remission and response to either bupropion (n=319) or placebo (n=257) in patients with major depressive disorder. Analyses were performed using conditional logistic regression. Significant association (gene-wide correction) was observed for remission following treatment with bupropion for a SNP within the serotonin receptor 2A gene (HTR2A rs2770296, p(corrected)=0.02). Response to bupropion treatment was significantly associated with a SNP in the dopamine transporter gene (rs6347, p(corrected)=0.013). Among the patients who received placebo, marginal association for remission was observed between a SNP in HTR2A (rs2296972, p(corrected)=0.055) as well as in the serotonin transporter gene (5-HTT or SLC6A4 rs4251417, p(corrected)=0.050). Placebo response was associated with SNPs in the glucocorticoid receptor gene (NR3C1; rs1048261, p(corrected)=0.040) and monoamine oxidase A gene (MAOA; rs6609257, p corrected=0.046). Although the above observations were significant after gene-wide corrections, none of these would be significant after a more conservative study-wide correction for multiple tests. These results suggest a possible role for HTR2A in remission to bupropion treatment. In accordance with bupropion pharmacology, dopamine transporter may play a role in response. The MAOA gene may be involved in placebo response.