title: SIRT1 gene is associated with major depressive disorder in the Japanese population.
abstract: BACKGROUND
  Many studies including our previous ones as to PROKR2 and CLOCK have suggested that circadian genes may be involved in the mechanisms of mood disorders and their treatment responses. Also several recent investigations have reported that SIRT1 plays an important role in the circadian system as conventional circadian clock genes, and also have some relation to dopaminergic metabolism. So we considered the SIRT1 gene to be a good candidate gene for the pathophysiology for MDD and SSRI responses in MDD, and conducted a case-control study using four tagging SNPs (450 MDD patients, including 261 patients treated by SSRIs and 766 controls).
  
  
  METHODS
  The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Marker-trait association analysis was used to evaluate allele and genotype association with the chi-square test, and haplotype association analysis was evaluated with a likelihood ratio test.
  
  
  RESULTS
  We found an association between rs10997875 in SIRT1 gene and MDD in the allele/genotype analysis. In addition, this significance of these associations survived Bonferroni correction. However, we did not find any association between SIRT1 gene and SSRI therapeutic response in MDD in the allele/genotype analysis or haplotype analysis.
  
  
  CONCLUSIONS
  A replication study using larger samples may be required for conclusive results, since our sample size was small.
  
  
  CONCLUSIONS
  Our results suggest that rs10997875 in SIRT1 gene may play a role in the pathophysiology of MDD in the Japanese population.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 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: Tsuyoshi
authors.initials: T
authors.lastname: Kitajima
authors.forename: Tomo
authors.initials: T
authors.lastname: Okochi
authors.forename: Takenori
authors.initials: T
authors.lastname: Okumura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsunoka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fukuo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naitoh
authors.forename: Wakako
authors.initials: W
authors.lastname: Umene-Nakano
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
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: D000483:Alleles; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D056564:Sirtuin 1 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D056564:Sirtuin 1; C447939:SIRT1 protein, human