The Combined Effects Of BDNF And GSK3B In A Chinese Population With Major Depressive Disorder

The combined effects of BDNF and GSK3B in a Chinese population with major depressive disorder (PartⅠ)Objective:Alterations in BDNF-signaling pathways may play an important role in the pathophysiological mechanisms of major depressive disorder (MDD). MDD is a complex disease that may have multiple causal genes, and these genes may interact with each other. Several lines of evidence suggest that gene-gene interactions may confer susceptibility to depression. The aim of this study was to analyze the relationship of single and combined effects of BDNF signal-transduction pathway genes with MDD in a Chinese population.Methods:We recruited a total of 447 patients with MDD and 432 age- and gender-matched control subjects. They were all Chinese Han origin. Five polymorphisms in 3 BDNF signal-transduction pathway genes (BDNF, GSK3B, and AKT1) were selected. The analyses of the gene-gene interactions were performed by UNPHASED (version 3.0).Result:Allelic associations between MDD patients and controls were observed for the polymorphism of GSK3B-rs6782799 if only uncorrected P is smaller than 0.05 and the corrected P is larger than 0.05 (χ2 = 5.24, uncorrected P = 0.022, corrected P = 0.107). Because allelic association was observed for GSK3B if uncorrected in this study, we used rs6782799 at the GSK3B locus as a conditioning marker for a gene-gene interaction test. Significant effects were obtained for the rs7124442-rs6782799 combination (χ2 =11.92, df = 2, uncorrected P = 0.003, corrected P = 0.011), and the rs6265-rs7124442-rs6782799 combination (χ2 = 14.45, df = 4, uncorrected P = 0.006, corrected P = 0.019) in the MDD group. When rs6782799 was applied as a conditioning marker, no interaction was observed between the AKT1 and GSK3B genes in the MDD group.Conclusions:To our knowledge, this is the first report on the combined effects of the BDNF and GSK3B genes in a Chinese population with MDD. BDNF and GSK3B may be causal genes for MDD patients of Han Chinese origin living in north China.Association between a functional polymorphism (rs6438552) of GSK3B and MDD in Chinese Han population Abstract(PartⅡ)Objective:Major depressive disorder (MDD) is one of the most prevalent and costly complex neuropsychiatric diseases. During the last decade, neuroimaging and postmortem studies in depressed adult patients demonstrated that decreased neurogenesis was involved in the underlying pathophysiology of MDD. GSK-3B participates in known biochemical pathways, playing a role as a susceptibility locus for multiple diseases, such as MDD. The aim of this study was to elucidate the relationship of GSK3B gene with MDD in a Chinese population.Methods:We recruited a total of 427 patients with MDD and 409 age- and gender-matched control subjects. They were all Chinese Han origin. The relationship between the SNP rs6438552 and MDD was investigated using a case-control design in a large sample partly overlap with the one used in our previous study. The analyses of the association were performed by UNPHASED (version 3.0).Result:Allelic association between MDD patients and controls was observed for the polymorphism of GSK3B-rs6438552 (χ2 = 4.59, df = 1, P=0.032, Odds ratio [OR] = 1.24, 95% CI [1.02–1.50]). The T allele of the GSK3B gene polymorphism was more common in the patient group compared with the control group.Conclusions:To our knowledge, this is the first report on the association between polymorphism and MDD in a overlap sample of Chinese Han population. GSK3B gene may be a causal gene for MDD patients of Han Chinese origin living in north China.