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An Association Study between Major Depression and Genes in the PI-3K Cascade

Author: LiuJinLi
Tutor: ZhangKeRang
School: Shanxi Medical
Course: Psychiatry and Mental Health
Keywords: Major Depression PI-3K pathway Gene polymorphism Association studies
CLC: R749.4
Type: Master's thesis
Year: 2008
Downloads: 127
Quote: 0
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Abstract


Objective: major depression is one of humanity's most severe mental disorders, persistent slow course, a heavy financial burden to families and society. Therefore, elucidating the pathogenesis of the disease, and to carry out the prevention, diagnosis and treatment, the medical community and the whole community needs to be urgently addressed. The etiology of the disease has not been elucidated, but the results of various studies show that major depression is a typical multi-gene complex disease, its occurrence is determined by genetic and environmental factors, about 50% of its heritability. The BDNF hypothesis that brain BDNF levels can cause depression, brain BDNF levels may produce antidepressant effects. BDNF and TrkB combined bootable intracellular signal transduction pathways such as phospholipase Cγ (PLC-γ), Ras-MAP kinase pathway, the phosphoinositide 3 - kinase (PI3-K) pathway, in vivo tests and nerve culture confirmed , BDNF mainly through PI3-K/Akt pathway elevate mood, improve cognitive function, enhance memory, improve the reconstruction of neurons to the treatment of depression. Our group uses gene channel strategy, systematic screening key on the PI-3K pathway gene SNPs, looking for major depression onset susceptibility gene or combination of genes. Methods: This study used a case - control analysis method, the northern 96 cases of patients with major depression and 96 with them strictly matched normal control is selected as the object of study. Polymerase chain reaction (PCR) and direct sequencing of the PCR products were genotyped. Application SPSS13.0 software for statistical analysis, genotype distribution χ2 test for comparison between gene combined effects analysis (Multifactor-Dimensionality Reduction, MDR) associated with a number of points. Results: (1) the Hardy-Weinberg genetic equilibrium test: In addition to the PIK3C3 outside (excluded), each polymorphism achieve genetic equilibrium (P gt; 0.05), selected sample group representation. Linkage disequilibrium analysis: selected gene single nucleotide polymorphism (SNP) are not located in the same linkage disequilibrium region (D 'lt; 0.70) 2 PI-3K pathway key genes associated with MD The: 2.1 PKB gene rs1130214 genotype in the MD group and the control group, the distribution of allele frequency difference was statistically significant (P values ??were 0.002,0.0003). 2.2 MDR found that the combined effects of a combination of: PKB/GSK-3β the incidence of major depression (P = 0.0325). Conclusion: 1 of PKB gene may be predisposing factors for major depression in Chinese Han population. 2. PKB/GSK-3β genes combined effects may be related to the pathogenesis of major depression. T allele of GSK-3β gene AG genotype combination will increase the risk of disease MD; containing PKB gene of PKB gene T allele of GSK-3β allele combination will increase the MD incidence dangerous .

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CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Affective psychosis
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