Association Of FKBP5Gene Polymorphisms And Life Events With Major Depressive Disorder

Objective:Impairments in hypothalamic-pituitary-adrenal (HPA) axis function and glucocorticoid (GC) exposure were proposed to participate in the etiology of major depressive disorder, and FKBP5could regulate the reactivity of HPA axis and GC sensitivity. To explore the relationship between rs1360780genetic variant in the gene FK506-binding proteins5(FKBP5) and the onset of major depressive disorder, clinic phenotypes at molecular level, as well as the impact of genetic factor and life events on the onset of major depressive disorder. To further study the pathogenesis of major depressive disorder and offer theoretical basis for screening risk population, early diagnosis, early intervention and individualized treatment, and provide new way for the development of new antidepressants.Methods:500patients were taken in the case-control study, which meet the DSM-IV diagnostic criteria for major depressive disorder, and550age-and gender-matched controls were recruited. HAMD-17was used to evaluate the severity of depression; and LES was used to assess the life events of patient and control groups. 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 FKBP5genotypes. All statistical analysis was performed using SPSS17.0statistical software, P<0.05was set as statistically significance.Result:1. Three genotypes of rs1360780genetic variant in the gene FKBP5were detected: CC, CT and TT. There was no statistical significance of the genotype distribution of CC, CT and TT between observed and expected frequency both in case group and control group, which was consistent with Hardy-Weinberg equilibrium.2. The significant differences between case and control group in genotypes and allele frequency distribution were only found in male (P<0.05), and subjects with T allele have a higher risk compared to those with C allele to develop major depressive disorder (OR=1.60S,95%CI1.095-2.360). When analyzed with the whole subjests or female only, no significant differences were detected between case and control group in genotypes and allele frequency distribution respectively (P>0.05).3. Sex, marital status, family history, age and first onset age in patients with different genotypes were not significantly different(P>0.05). 4. Subjects with TT genotype had a higher score of genital symptoms compared to those with CT genotype and CC genotype, and those differences had statistical significance (P<0.05). HAMD total score, retard factor, sleep factor, Maier factor, anxiety/somatization factor and core factor in patients with different genotypes were not significantly different (P>0.05).5. Life events had influence on the onset of major depressive disorder (P<0.05), rs1360780genetic variant in the gene FKBP5and the interaction of these two factors had no influence on the onset of major depressive disorder (P>0.05).Conclusion:1. There may be significant correlation between FKBP5gene polymorphisms in locus rs1360780and the onset of major depressive disorder in male, and subjects with T allele have a higher risk compared to those with C allele to develop major depressive disorder (OR=1.608,95%CI1.095-2.360). When analyzed with the whole subjests or female only, no significant associations were detected between FKBP5gene polymorphisms in locus rs1360780and the onset of major depressive disorder respectively.2. Sex, marital status, family history, age and first onset age in patients had no association with FKBP5gene polymorphisms in locus rs1360780.3. FKBP5gene polymorphisms may be associated with genital symptoms in retard symptom, but severity of depression, retard symptom, sleep symptom, Maier symptom, anxiety/somatization symptom and core symptom had no association with FKBP5gene polymorphisms in locus rs1360780.4. Life events had influence on the onset of major depressive disorder, rs1360780genetic variant in the gene FKBP5and the interaction of these two factors had no influence on the onset of major depressive disorder.