title: Association analysis of SIGMAR1 with major depressive disorder and SSRI response.
abstract: BACKGROUND
  Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline).
  
  
  METHODS
  We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis.
  
  
  RESULTS
  In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples.
  
  
  CONCLUSIONS
  Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. tarok@fujita-hu.ac.jp
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Reiji
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Tomo
authors.initials: T
authors.lastname: Okochi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fukuo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kitajima
authors.forename: Takenori
authors.initials: T
authors.lastname: Okumura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsunoka
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Wakako
authors.initials: W
authors.lastname: Umene-Nakano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naitoh
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017480:Receptors, sigma / Q000235:genetics*; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000097605:Sigma-1 Receptor
chemical_list: D016666:Fluvoxamine; D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000097605:Sigma-1 Receptor