title: Interaction of 5-HTT and HTR1A gene polymorphisms in treatment responses to mirtazapine in patients with major depressive disorder.
abstract: We tested for the association of HTR1A and 5-HTT genetic polymorphisms with treatment response to mirtazapine and evaluated the interactive effect between the polymorphisms in 283 patients with major depressive disorder. Korean subjects with diagnosis of major depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. Clinical symptoms were evaluated using the 17-item Hamilton Depression Rating (HAMD-17) Scale at baseline and after 1, 2, 4, 8, and 12 weeks of treatment with mirtazapine. The genetic association of 5-HTTLPR and HTR1A+272G>A with treatment response was analyzed. We found a significant association of the 12.12-repeat genotype of 5-HTT various number tandem repeat (VNTR) with a large percentage decline in HAMD-17 Scale score after 4, 8, and 12 weeks of treatment with mirtazapine. We also found that the frequency of the 12.12-repeat genotype was higher in responders than in nonresponders at week 8. The HTR1A+272GG genotype was significantly associated with a large percentage decline in HAMD-17 Scale score at 4, 8, and 12 weeks, although the genotypic frequencies were comparable between responders and nonresponders during the study period. Patients with the 12.12-repeat 5-HTT VNTR and GG of HTR1A+272G>A showed the highest HAMD-17 Scale percentage reduction during the study period and a better treatment response status after 4 weeks. These results suggest that the interaction between HTR1A+272G>A and 5-HTT VNTR is involved in the response to mirtazapine treatment and that a combination of these may be a useful marker for predicting treatment response to mirtazapine.
authors.affiliation: From the *Department of Medical Bioscience, Graduate School, Soonchunhyang University, Bucheon; †Department of Psychiatry, College of Medicine, Soonchunhyang University; ‡Department of Psychiatry, College of Medicine, and §Pharmacogenomic Research Center for Psychotropic Drugs, Korea University, Seoul, Republic of Korea.
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Cha
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Won
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Ham
authors.forename: Bohye
authors.initials: B
authors.lastname: Kim
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D011110:Polymorphism, Genetic / Q000235:genetics*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; C583518:HTR1A protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D008803:Mianserin; D000078785:Mirtazapine