GABRB2基因启动子区DNA甲基化与精神分裂症及其治疗的关系☆

2016-08-03樊梅禹顺英

中国神经精神疾病杂志 2016年4期

樊梅　　禹顺英

樊梅*禹顺英*

目的探讨γ-氨基丁酸A型受体β2亚基（gamma-aminobutyric acid type A receptor beta2 subunit，GA⁃BRB2）基因启动子区DNA甲基化水平与精神分裂症及其药物治疗的关系。方法纳入精神分裂症患者53例和正常对照53名，采用MassARRY EpiTYPER DNA甲基化分析技术检测所有受试者外周血GABRB2基因启动子区DNA甲基化水平。患者组中12例在药物治疗8周后再次检测该基因启动子区DNA甲基化水平。结果患者组与对照组外周血GABRB2基因启动子区总甲基化和各CpG位点的甲基化水平组间差异无统计学意义（P＞0.05）。经性别分层分析，患者组男性CpG_28位点的甲基化水平较对照组男性降低［（0.215±0.084）vs.（0.264± 0.103），P＜0.05］。治疗后患者组外周血GABRB2基因启动子区总DNA甲基化水平较治疗前降低［（0.088±0.037）vs.（0.121±0.063），P＜0.01］，治疗前后各CpG位点甲基化水平差异无统计学意义（P＞0.05）。结论抗精神病药物治疗可降低精神分裂症患者外周血中GABRB2基因启动子区DNA甲基化水平，提示基因启动子区DNA甲基化可能参与抗精神病药物治疗的作用机制。

DNA甲基化精神分裂症 GABRB2基因

【Abstract】Objective Gamma amino butyric acid（GABA）signaling pathway related genes mRNA expression and promoter methylation of GABRB2 gene in peripheral blood were investigated to explore the mechanisms involved in schizophrenia（SZ）and antipsychotics treatment.Methods DNA was isolated from blood samples of 53 SZ patients and 53 gender-and age-matched healthy controls.12 out of 25 SZ patients were followed 8 weeks antipsychotic treatment. The quantitative GABRB2 promoter methylation was analyzed using the high-throughput mass spectrometry on matrix-as⁃sisted laser desorption/ionization time-of-flight（MALDI-TOF）mass array before and after treatment.Results The GA⁃BRB2 promoter methylation pattern of case and control group was not significantly different（P＞0.05）.However，signifi⁃cant differences of the methylation levels of CpG_28 in the GABRB2 promoter between two groups were found in males［（0.215±0.084）vs.（0.264±0.103），P＜0.05］.After 8 weeks antipsychotics treatment，a significant decrease of GABRB2 pro⁃moter methylatin was detected in the patients［（0.088±0.037）vs.（0.121±0.063），P＜0.01］.Conclusion A down regulation of GABRB2 promoter methylation in blood of SZ patients after-treatment supports that GABRB2 promoter methylation in blood may be associated with the mechanisms of antipsychotics treatment in SZ.

【Key words】DNA methylation Schizophrenia GABRB2 gene

γ-氨基丁酸（gamma-aminobutyric acid，GABA）能信号缺陷假说是精神分裂症（schizophrenia，SZ）发病机制的重要假说之一。目前有研究报道SZ患者外周血中存在GABAA受体β2亚基（GABAAre⁃ceptor β2subunit，GABRB2）基因外显子区CpG位点高甲基化［1］。启动子区CpG岛（CpG islands，CGIs）中的 5-甲基胞嘧啶（5-methylcytosine，5-mC）会阻碍转录因子复合体与DNA结合，因而DNA甲基化一般与基因沉默相关联［2］。目前尚未有关于SZ的研究报道GABRB2基因启动子区DNA甲基化异常。本研究拟检测精神分裂症患者外周血GABRB2基因启动子区DNA甲基化水平，探索其与SZ及药物治疗的关系。