Li Jun, You Yang, Yue Weihua, Yu Hao, Lu Tianlan, Wu Zhiliu, Jia Meixiang, Ruan Yanyan, Liu Jing, Zhang Dai, Wang Lifang
Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China.
Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, PR China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, PR China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, PR China.
Neurosci Lett. 2016 Jan 1;610:182-6. doi: 10.1016/j.neulet.2015.10.074. Epub 2015 Nov 10.
Autism spectrum disorder (ASD) is a group of severe neurodevelopmental disorders. Epigenetic factors play a critical role in the etiology of ASD. Enhancer of zest homolog 2 (EZH2), which encodes a histone methyltransferase, plays an important role in the process of chromatin remodeling during neurodevelopment. Further, EZH2 is located in chromosome 7q35-36, which is one of the linkage regions for autism. However, the genetic relationship between autism and EZH2 remains unclear. To investigate the association between EZH2 and autism in Chinese Han population, we performed a family-based association study between autism and three tagged single nucleotide polymorphisms (SNPs) that covered 95.4% of the whole region of EZH2. In the discovery cohort of 239 trios, two SNPs (rs740949 and rs6464926) showed a significant association with autism. To decrease false positive results, we expanded the sample size to 427 trios. A SNP (rs6464926) was significantly associated with autism even after Bonferroni correction (p=0.008). Haplotype G-T (rs740949 and rs6464926) was a risk factor for autism (Z=2.655, p=0.008, Global p=0.024). In silico function prediction for SNPs indicated that these two SNPs might be regulatory SNPs. Expression pattern of EZH2 showed that it is highly expressed in human embryonic brains. In conclusion, our findings demonstrate that EZH2 might contribute to the genetic etiology of autism in Chinese Han population.
自闭症谱系障碍（ASD）是一组严重的神经发育障碍。表观遗传因素在ASD的病因中起着关键作用。编码组蛋白甲基转移酶的zest同源物2增强子（EZH2）在神经发育过程中的染色质重塑过程中起重要作用。此外，EZH2位于7号染色体的7q35 - 36区域，该区域是自闭症的连锁区域之一。然而，自闭症与EZH2之间的遗传关系仍不清楚。为了研究中国汉族人群中EZH2与自闭症之间的关联，我们对自闭症与覆盖EZH2整个区域95.4%的三个标签单核苷酸多态性（SNP）进行了基于家系的关联研究。在239个三联体的发现队列中，两个SNP（rs740949和rs6464926）与自闭症显示出显著关联。为了减少假阳性结果，我们将样本量扩大到427个三联体。即使经过Bonferroni校正，一个SNP（rs6464926）仍与自闭症显著相关（p = 0.008）。单倍型G - T（rs740949和rs6464926）是自闭症的一个风险因素（Z = 2.655，p = 0.008，全局p = 0.024）。对SNP的计算机功能预测表明，这两个SNP可能是调控性SNP。EZH2的表达模式表明它在人类胚胎大脑中高度表达。总之，我们的研究结果表明，EZH2可能在中国汉族人群自闭症的遗传病因中起作用。
