title: Association of ARRB1 polymorphisms with the risk of major depressive disorder and with treatment response to mirtazapine.
abstract: β-Arrestin 1 is known to be involved in the pathophysiology of major depressive disorder (MDD) and in the underlying mechanism of action of antidepressant therapies. After we screened 39 ARRB1 polymorphisms, we investigated the associations of seven ARRB1 single-nucleotide polymorphisms (SNPs) with the risk of MDD in 270 patients with MDD and 204 normal subjects, and with mirtazapine treatment response in patients with MDD. The genotype distributions of -132C>T and IVS1+85T>C showed significant deviations from Hardy-Weinberg equilibrium in patients with MDD but not in normal subjects. After four and 12 weeks of mirtazapine treatment, the proportion of haplotype 1 (ht1) carriers was significantly higher in remitters than in non-remitters after corrections for multiple comparisons (corrected p=0.006 and 0.014 at four and 12 weeks, respectively). After eight and 12 weeks of treatment, scores on the 21-item Hamilton Depression Rating Scale (HAMD21) were significantly lower in patients with MDD with ARRB1 ht1 than in those without ht1. Similarly, after 8 and 12 weeks of treatment, the percent reduction in HAMD21 scores was significantly higher in patients with MDD with ARRB1 ht1 than in those without ht1. The ARRB1 polymorphisms represent promising genetic markers for the prediction of treatment responses to mirtazapine.
authors.affiliation: Department of Medical Bioscience, Soonchunhyang University, Bucheon, Republic of Korea.
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.affiliation: Pharmacogenetic Research Center for Psychotropic Drugs, Korea University, Seoul, Korea Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Won
authors.affiliation: Department of psychiatry, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Pharmacogenetic Research Center for Psychotropic Drugs, Korea University, Seoul, Korea Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Ham
authors.affiliation: Pharmacogenetic Research Center for Psychotropic Drugs, Korea University, Seoul, Korea Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Yong-Gu
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Pharmacogenetic Research Center for Psychotropic Drugs, Korea University, Seoul, Korea Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea leeminso@korea.ac.kr.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D019390:Arrestins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D055815:Young Adult; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; D000929:Antidepressive Agents, Tricyclic; D019390:Arrestins; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D008803:Mianserin; D000078785:Mirtazapine
keywords: major depressive disorder; mirtazapine; polymorphism; treatment response; β-Arrestin 1