A Correlational Study Of BDNF (Val66Met) Gene Polymorphisms, Life Events And Major Depressive Disorder

Objective:To explore the correlation of brain-derived neurotrophic factor (BDNF) gene polymorphisms (Val66Met) and the onset of major depression; and to investigate the relationship between BDNF genotypes and the incidence of major depression, clinic phenotypes at molecular level as well as the impact of genetic factor and life events on the severity of depression. To further study the pathogenesis of major depression and offer theoretical basis for early diagnosis, individualized treatment and prevention of depression.Methods:A case-control method was taken 250 patients, which meet the DSM-â…£diagnostic criteria for major depressive disorder, and 250 age- and gender-matched controls were recruited. HAMD-17 was used to evaluate the severity of depression; and LES was used to assess the life events of patient group. Peripheral blood of all the objects was collected, and genomic DNA was extracted. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) was used to determine BDNF (Val66Met) genotypes. All statistical analysis was performed using SPSS 13.0 statistical software. Hardy-Weinberg equilibrium was used to test the genotype and allele frequency distribution. Hierarchical linear regression analysis was adopted to analysis the interaction of BDNF gene polymorphisms and life events on the severity of depression. P<0.05 was set as statistically significance.Result:1. Three genotypes of BDNF Val66Met were detected:Val/Val, Val/Met and Met/Met. There's not statiscal significance of the genotype distribution of Val/Val, Val/Met, Met/Met between observed and expected frequency both in case group and control group, which were consistent with Hardy-Weinberg equilibrium.2. There was not significant differences of genetype distribution between the patients and controls (P=0.0132), so was the allele frequency (P=0.057).3. The occurrence of life events among the three genotypes was significantly different (P=0.009), and the number of patients carrying Met allele with stress events is 1.19 times that of patients with Val/Val (P=0.003). There were still significant differences after correcting the factor of life events.4. HAMD total score in patients with different genotypes was not significantly different. The patients with Val/Val genotype had lower scores in retard factor, core factor and Maier factor (P<0.05) than the Met carriers, and the scores of depressive mood and losing interest were significantly lower in patients with Val/Val genotype (P=0.000).5. Neither life events nor BDNF polymorphism individually predicted HAMD scores. however, the interaction of them significantly predicted the severity of depression (P=0.002).Conclusion:1. No significant association was found between BDNF Val66Met polymorphism and the onset of major depression in Tianjin.2. Compared with Met carriers. Val/Val type of this polymorphism was less susceptible to the stress events, and was more suffering from endogenous depressive disorder.3. BDNF Val66Met polymorphism may be associated with core symptom, retardation symptom and Maier symptom of major depression.4. Neither life events nor BDNF Val66Met polymorphism individually predicted the severity of depression, but the interaction of the two factors did.