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 neurotrophic 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 methylation rate was identified in 17 and 8 CpG units in BDNF promoter][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][CpG units 4,7,10,35,and BDNF promoter Ⅳ CpG units 11.12,14 could be clustered.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 controls (P＜0.05).Conclusions The DNA methylation rate in BDNF pronoter Ⅰ CpG unit 5.6 and Ⅳ CpG units 3 and 15 may be used as potential biomarkers of ASD.
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