An Association Study Between Major Depression And Genes In The PI-3K Cascade

Objective: Major depression is the most common mental disorder. Since the disorder causes heavy economical and social burdens to families and societies, it is very important to establish a procedure of treating and preventing major depression, and the investigation of the susceptibility genes for major depression becomes noticeable generally. Though its molecular etiology remains unknown, the data from twin, adoption and family studies have clearly demonstrated that schizophrenia is a representative complex disorder .Its pathogenesy involved genetics and environmental factors and its heritability about 50%.In humans, brain BDNF levels have been found to be reduced in postmortem samples from depressed patients, and antidepressant therapy restores brain BDNF levels to the normal range. BDNF and its tyrosine kinase receptor TrkB can active three signal transduction cascades—the PLC-γcascade ,the mitogen-activated protein kinase, and the phosphatidylinositol-3 kinase casecade(PI3K). In vivo,PI3K cascade is included in the survival of neurons in the brain and the therapy of major depression. Candidate gene strategy wad taken in our work and we systematically screened SNPs of genes on metabolic pathway of PI3K to analyze the association between genes on the PI3K cascade and major depression.Methods: In the present study, case-control study was taken. A total of 96 patients with paranoid schizophrenia meeting ICD-10 criteria and 96 matched normal controls were recruited from Beijing, north China. All subjects were unrelated Han Chinese and gave written informed consent. All statistical analysis was performed using SPSS 13.0 statistical software. The genotype and allele frequency distribution were compared withχ2 analysis. MDR is used to analysis the interaction of SNPs.Results: (1)There was significant differences of gene genotypic or allelic frequencies of PKB between the patients and controls(P=0.002). (2) Using Multifactor dimensionality reduction method, one combination that PKB/GSK-3βwere detected to be significantly susceptible to major depression(P=0.03).Conclution: We concluded that the combination of PKB and GSK-3βmay play a major role in major depression pathogenesis in the Chinese Han population. The combination of T-AG may increase the risk of MD. PKB gene is one possible suspected gene for major depression and T allel may increase the risk of MD.