Association Of SIRT1 Gene Polymorphism With Depressive Symptoms And Response In The Chinese Han Population With Major Depressive Disorder

Objective:To explore the association between polymorphisms SIRT1 gene and the clinical symptoms of depressive disorder,and the efficacy of antidepressant treatment(SSRI)in Chinese Han major disorder(MDD)patients.Methods:A total of 350 MDD patients diagnosed by DSM-IV were enrolled.All of the patients were treated with SSRI over 8 weeks and we elevated the clinical data at week 1,2,4and 8.The clinical symptoms and efficacy of antidepressant treatment were evaluated by the total of Hamilton Depression scale-17(HAMD-17).The single nucleotide polymorphisms(SNPs)of gene were detected by mass spectrometry platform sequencing.The SNPs included rs10997875,rs2273773 and rs4746720 in SIRT1 gene,rs12415800 near the SIRT1 gene.The quantitative traits of clinical symptoms of patients and SNPs were analyzed by Unphased 3.0.8 software.Statistical analysis were performed using SPSS17.0 software.Results:1.Hardy-Weinberg genetic balance(HWE)testAll SNPs,rs10997875,rs2273773,rs4746720 and rs12415800 in SIRT1 and near SIRT1 gene were detected in this sample were in HWE(P>0.05),which indicated the samples were represent the population.2.General demography data analysisThe differences of sex,age,marital status,family history,and suicide history in the different groups were analyzed.There were differences of the sexes(P=0.032),in the marital status(P=0.026)and suicide history(P=0.005)in the effective group vs.the invalid group.There were no significantly difference of the rest general data between the two groups(P>0.05).3.Quantitative traits of clinical symptomsThe polymorphisms rs10997875 was associated with somatic symptoms genera.(genotype P=0.031).The polymorphisms rs2273773 were associated with cognitive symptoms(genotype P=0.049)and suicide(genotype P=0.039).The polymorphisms rs4746720 were associated with insomnia(genotype P=0.044),guilt feelings(genotype P=0.038,allele P=0.048)and suicide(genotype P=0.047).The polymorphisms rs12415800 was associated with somatic symptoms(P=0.041),and genital symptom(genotype P=0.040 allele P=0.034).The interaction of rs12415800-rs10997875 was associated with insomnia(allele P=0.047),somatic symptoms(genotype P=0.031),and genital symptom(genotype P=0.041).The interaction of rs12415800-rs4746720 was associated with cognition(allele P=0.046),weight(genotype P=0.040 allele P=0.048),suicide(allele P=0.043),and genital symptom(genotype P=0.029 allele P=0.034).The interaction of rs12415800-rs10997875-rs4746720 was associated with suicide(allele P=0.047)insomnia middle(genotype P=0.020 and allele P=0.024),and somatic symptoms(genotype P=0.026 allele P=0.042).4.Association analysis efficacyAssociation between rs12415800 genotype and efficacy of SSRI was found in our sample(P=0.040),and the carried G(GG+GA)showed a resistance to antidepressive treatment with SSRI.No significantly associations of other SNPs were found in our sample.Conclusion:1.SIRT1 rs10997875,rs2273773,rs4746720 and the near SIRT1 rs12415800 were associated with the symptoms of MDD.2.The interaction of rs12415800-rs10997875,rs12415800-rs4746720 and rs12415800-rs10997875-rs4746720 were associated with the symptoms of MDD.3.The rs12415800 near SIRT1 gene may be associated with SSRI in Chinese Han MDD patients.