SIRT1 gene is associated with major depressive disorder in the Japanese population.
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.
Kishi
Taro
T
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. tarok@fujita-hu.ac.jp
Yoshimura
Reiji
R
Kitajima
Tsuyoshi
T
Okochi
Tomo
T
Okumura
Takenori
T
Tsunoka
Tomoko
T
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Kawashima
Kunihiro
K
Fukuo
Yasuhisa
Y
Naitoh
Hiroshi
H
Umene-Nakano
Wakako
W
Inada
Toshiya
T
Nakamura
Jun
J
Ozaki
Norio
N
Iwata
Nakao
N
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
D017367:Selective Serotonin Reuptake Inhibitors; D056564:Sirtuin 1; C447939:SIRT1 protein, human