脑源性神经营养因子启动子区甲基化与孤独症谱系障碍关系初探  

The study on the association of the methylation in the promoter region of brain derived neurotrophic factor with autism spectrum disorders

作　　者：周家秀[1] 丁明[2] 崔冬[3] 张琳琳[1] 周甄会[1] 秦尚够[1] 廖汝琴 王艳 何福生 杨峰[5] 王明帮 

机构地区：[1]广东省深圳市儿童医院心理科,深圳518038 [2]广东省深圳市儿童医院科教科 [3]广东省深圳市儿童医院儿科研究所 [4]深圳市众循精准医学研究院自闭症基因组研究所 [5]广东省深圳市儿童医院言语治疗科

出　　处：《中国神经精神疾病杂志》2017年第2期98-102,共5页Chinese Journal of Nervous and Mental Diseases

基　　金：深圳市科创委基础研究项目(编号:JCYJ20130401114111453);深圳市科技创新委员会基础研究项目(编号:JCYJ20140416141331555)

摘　　要：目的通过比较孤独症谱系障碍(autism spectrum disorders,ASD)患者和正常对照脑源性神经营养因子(brain derived neurotrophic factor,BDNF)基因启动子Ⅰ区和Ⅳ区各CpG单元甲基化率,探讨ASD可能的发病机制。方法选取ASD患者12例及正常对照12名,利用飞行时间质谱法检测全血中BDNF基因启动子Ⅰ和Ⅳ区各CpG单元甲基化率,并分析其相关性距离、进化关系,比较两组各单元甲基化率。结果在BDNF启动子Ⅰ区和Ⅳ区分别检测到17个和8个CpG单元的甲基化率。ASD患者组BDNF启动子Ⅰ区中CpG单元4、7、10、35,以及BDNF启动子Ⅳ区CpG单元11.12、14相关性距离较近,聚类成比较小的分支。ASD患者BDNF启动子Ⅰ区CpG单元5.6甲基化率低于对照组(P<0.05),Ⅳ区CpG单元3和15甲基化率高于对照组(P<0.05)。结论 ASD患者BDNF启动子Ⅰ区CpG单元5.6和Ⅳ区CpG单元3和15甲基化率在ASD患者组和对照组差异显著,提示BDNF启动子甲基化可作为ASD潜在的生物标志物深入研究。Objective The aim of present study was to detect methylation rate of CpG unit of brain derived neurotrophie factor （BDNF） promoter and to study the epigenetic mechanism of autism spectrum disorders （ASD）. Methods Total of 12 ASD patients and 12 healthy controls were recruited. The methylation rate of CpG unit in BDNF promoter I and IV were detected using Sequenom MassArray method. The methylation model, correlationship, evolutionary relationship of CpG units in BDNF promoter I and IV were detected and compared between ASD patients and healthy controls. Results The metbylation rate was identified in 17 and 8 CpG units in BDNF promoter I and BDNF promoter IV. A close correlation distance was detected in BDNF promoter I CpG units 4, 7, 10, 35, and BDNF promoter IV CpG units 11.12, 14. BDNF promoter I CpG units 4, 7, 10, 35, and BDNF promoter IV CpG units 11.12, 14 could beclustered. ASD patients had a significant lower methylation rate in BDNF promoter I CpG unit 5.6 and IV CpG units 3 and 15 compare with healthy eontrols （P〈0.05）. Conclusions The DNA methylation rate in BDNF promoter I CpG unit 5.6 and IV CpG units 3 and 15 may be used as potential biomarkers of ASD.

关 键 词：孤独症谱系障碍脑源性神经营养因子启动子 甲基化 

分 类 号：R749.94[医药卫生—神经病学与精神病学]