Association Of Glycogen Synthase Kinase-3βGene Polymorphisms And Life Events With Major Depressive Disorder

Objective:To explore the association of Glycogen synthase kinase-3p (GSK-3β) gene polymorphisms and the onset of major depressive disorder (MDD), clinical symptoms and severity of depression; also to investigate the correlation between life events and MDD, analysis the influence of interaction between GSK-3β polymorphisms and life events on MDD. To further study the pathogenesis of major depressive disorder and provide theoretical basis for early diagnosis and preventing MDD.Methods:A case-control association study was performed, including500patients which meet the diagnostic and statistical manual of mental disorders in the fourth edition (DSM-IV) criteria for major depressive disorder (MDD), and550age-and gender-matched healthy controls. HAMD-17was used to evaluate the severity of depression. LES was adopted to assess the life events of case group and control group. Peripheral blood of all the objects was collected, and extracted genomic DNA of blood samples. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) was used to detect the polymorphism of rs334558loci of GSK-3p genotypes. Hardy-Weinberg equilibrium was used to test the genotype and allele frequency distribution. SPSS19.0statistical software was used for statistical analysis.Results:1. Three genotypes of GSK-3β rs334558were detected:CC, CT and TT. There was no statiscal significance of the genotype distribution of CC, CT and TT between observed and expected frequency both in case group and control group (P>0.05), which indicate the consistency with Hardy-Weinberg equilibrium.2. The frequency distribution of genotypes and alleles of GSK-3β rs334558between MDD patients and controls had no significant difference (.P>0.05). However, we had found the significant differences including genotypes and alleles only in female (P<0.05) but not male (P>0.05).In female, CC genotype was a protective factor for MDD(P<0.05,OR=0.528,95%CI0.323±0.861), and T allele was a risk factor for MDD compared with C allele (P<0.05, OR=1.363,95%CI1.100±1.688).3. The frequency distribution of genotypes was not related to demography including sex, family history, marriage, age and age of the first onset in MDD patients (P>0.05).4. There was significant difference in psychogenic anxiety symptom score between CC and other genotype (P<0.05), patients with CC gene had higher anxiety score. But HAMD total score, retard factor, core factor, maier factor, sleeping symptom factor, anxiety/somatization factor in patients with different genotypes had no significant differences (P>0.05).5. The LES score of case group was higher than that of control group (P<0.05). The LES score of different genotypes had no significant difference in case group (P>0.05). When the patients were classified into mild-moderate depression and severe depression groups, LES score in different subgroups was significantly difference, severe depression group had higher LES score compared with mild-moderate depression group (P<0.05).6. There was no interaction of GSK-3β rs334558polymorphisms and life events related to MDD (P>0.05).Conclusion:1. GSK-3β rs334558polymorphisms may have gender specific in the pathogenesis of MDD. Only in female, there was a significant association between GSK-3β rs334558polymorphisms and the onset of MDD in Tianjin, CC genotype was a protective factor for MDD, T allele was a risk factor for MDD.2. There was no association of GSK-3β rs334558polymorphisms in patients’ demography, including sex, family history, marriage, age and age of the first onset of MDD.3. GSK-3β rs334558polymorphisms may be associated with psychogenic anxiety symptom of MDD, but there were no association between genotype and severity of MDD, retard factor, core factor, maier factor, sleeping symptom factor, anxiety/somatization factor.4. Life events play a role in conferring risk of MDD, the patients with MDD may be experiencedm more life event.What’s more, the severity of life events had corelation with the severity of MDD.5. There was no interaction of GSK-3β rs334558polymorphisms and life events related to MDD.