脑源性神经营养因子基因启动子区DNA甲基化与惊恐障碍的关联研究

Association study of the BDNF promoter methylation status with panic disorder

目的探讨惊恐障碍与脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)基因启动子区DNA甲基化水平的关系,并分析BDNF基因甲基化水平与疾病严重程度的关系。方法采用MethylTarget技术对111例惊恐障碍患者和130例正常对照进行BDNF甲基化水平检测,同时采用惊恐障碍严重度量表(panic disorder severity scale,PDSS)、汉密尔顿焦虑量表(HAMA)和汉密尔顿抑郁量表(HAMD)评定患者的疾病严重程度。结果(1)惊恐障碍患者BDNF基因DNA甲基化水平与正常对照组比较差异无统计学意义(OR=1.087,95%CI=0.849~1.391,P>0.05);两者在BDNF基因启动子区的7个CpG片段甲基化水平差异也均无统计学意义(P>0.05)。(2)惊恐障碍患者BDNF基因启动子区BDNF_1、BDNF_2、BDNF_3、BDNF_4、BDNF_5、BDNF_7 CpG片段及BDNF基因的DNA甲基化水平与其HAMD总分呈不同程度的正相关(r=0.194~0.364)。而惊恐障碍患者BDNF基因及各CpG片段甲基化水平与PDSS和HAMA总分均未发现有统计学意义的相关(P>0.05)。结论BDNF基因启动子区DNA甲基化与惊恐障碍不存在关联,但可能与惊恐障碍伴有的抑郁情绪有关。

Objective To explore whether brain-derived neurotrophic factor(BDNF)promoter methylation status is associated with panic disorder(PD),and then assess the effect of the BDNF gene methylation status on the severity of clinical symptoms in PD.Methods The methylation levels of the BDNF gene were compared between 111 patients with PD and 130 matched healthy controls using MethylTarget approach.In addition,the panic disorder severity scale(PDSS),Hamilton anxiety rating scale(HAM-A),and Hamilton depression rating scale(HAM-D)were respectively assessed to all subjects.Results(1)The result showed that 7 CpG regions from the promoter regions of the BDNF gene were sequenced.However,there was no statistically significant differences between cases and controls in terms of BDNF DNA methylation status(OR=1.087,95%CI=0.849-1.391,P>0.05).(2)Spearman correlation analysis revealed that the hypermethylation of BDNF gene was significantly associated with the severity of the depressive symptoms in PD patients(all P<0.05).The methylation levels of BDNF gene was not significantly related to the severity of anxiety and panic in PD patients(all P>0.05).Conclusion No association between BDNF promoter methylation status and panic disorder is found in Chinese Han population,but BDNF promoter methylation status may be related to the severity of depressive symptoms in patient with panic disorder.