Chromatin remodeling gene EZH2 involved in the genetic etiology of autism in Chinese Han population
Chromatin remodeling gene EZH2 involved in the genetic etiology of autism in Chinese Han population
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染色质重塑基因EZH2参与中国汉族自闭症遗传病因
DOI：
10.1016/j.neulet.2015.10.074
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发表时间：
2016-01-01
影响因子：
2.5
通讯作者：
Wang, Lifang
中科院分区：
文献类型：
--
作者：
Li, Jun;You, Yang;Wang, Lifang
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的病因学中起关键作用。zest homolog 2的增强子（Enhancer of zest homolog 2, EZH2）编码组蛋白甲基转移酶，在神经发育过程中染色质重塑过程中起重要作用。此外，EZH2位于染色体7q35-36，这是自闭症的连锁区域之一。然而，自闭症和EZH2之间的遗传关系尚不清楚。为了研究EZH2与中国汉族人群自闭症之间的关系，我们进行了一项基于家庭的研究，研究了三个标记的单核苷酸多态性（snp）与自闭症之间的关系，这些snp覆盖了EZH2整个区域的95.4%。在239个三人组的发现队列中，两个snp （rs740949和rs6464926）显示出与自闭症的显著关联。为了减少假阳性结果，我们将样本量扩大到427组。即使在Bonferroni校正后，SNP （rs6464926）也与自闭症显著相关（p = 0.008）。单倍型G-T （rs740949和rs6464926）是自闭症的危险因素（Z=2.655, p = 0.008, Global p = 0.024）。单核苷酸多态性的功能预测表明，这两个单核苷酸多态性可能是调控单核苷酸多态性。EZH2的表达模式显示其在人胚胎脑中高表达。总之，我们的研究结果表明EZH2可能参与了中国汉族人群自闭症的遗传病因。2015爱思唯尔爱尔兰有限公司版权所有。
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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.