ABSTRACT
Objective:To explore the relationship between rs3758391 polymorphism of SIRT1 gene and depressive symptoms, and to further understand the role of SIRT1 gene in major depressive disorder. Methods:A total of 323 patients with major depressive disorder were retrospectively collected from the Jinhua Second Hospital, Wenzhou Kangning Hospital and Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine. A total of 347 healthy subjects were also recruited. Depressive symptoms were evaluated by using the Hamilton Depression Scale (HAMD), and rs3758391 polymorphism was genotyped by using the TaqMan SNP genotyping Assay. The effect of rs3758391 polymorphism on the expression of SIRT1 mRNA in brain was analyzed by BRAINEAS database, and the difference of depressive symptom severity among three genotypes at rs3758391 polymorphism was compared by multivariate analysis of variance. Results:The frequencies of C and T alleles of rs3758391 polymorphism in SIRT1 gene were 18.7% and 81.3% in the case group, and 14.3% and 85.7% in the control group, respectively. The allelic distribution frequencies between the two groups were significantly different (χ2=4.86, P=0.03). There were significant differences in mood, cognitive impairment and HAMD scores among patients with different genotypes of rs3758391 polymorphism (P<0.05). The results of eQTL analysis showed that rs3758391 polymorphism was significantly correlated with the expression of SIRT1 gene in occipital cortex (OCTX) (P=0.003). Conclusion:rs3758391 polymorphism of SIRT1 gene may be a risk factor for major depressive disorder in Chinese Han population, and is associated with the severity of depressive symptoms, especially with emotional symptoms and cognitive impairment.