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自闭症谱系障碍中长链非编码 RNA 的表达改变。

Altered expression of lncRNAs in autism spectrum disorder.

机构信息

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Metab Brain Dis. 2021 Jun;36(5):983-990. doi: 10.1007/s11011-021-00681-z. Epub 2021 Feb 15.

Abstract

Long non-coding RNAs (lncRNAs) have been recognized as an important epigenetic factor in the evolution of neuropsychiatric conditions. We have selected five lncRNAs (DISC2, PRKAR2A-AS1, LOC105375675, LRRC2-AS1, and LOC101928237) to measure their expression in blood samples of children with autism spectrum disorder (ASD) versus children with normal development. Expressions of DISC2, PRKAR2A-AS1 and LOC101928237 have been enhanced in ASD cases compared with healthy children (Posterior Beta = 2.508, P value<0.0001; Posterior Beta = 2.793, P value = 0.014 and Posterior Beta = 1.646, P value <0.0001, respectively). On the other hand, expression of LRRC2-AS1 has been lower in ASD patients compared with controls (Posterior Beta = -3.781, P value<0.0001). Remarkably, expression of DISC2 and PRKAR2A-AS1 have been lower in girls compared with boys (Posterior Beta = -0.982, P value<0.0001 and Posterior Beta = -0.135, P value<0.0001, respectively). In addition, expression of DISC2 has been lower in ASD cases aged more than 6 compared with those aged less than 6 years (Posterior Beta = -0.876, P value = 0.003). DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 had the area under curve (AUC) values of 0.76, 0.90, 0.92, and 0.79 in distinguishing between ASD and healthy children. Expression levels of none of DISC2, LOC101928237, LOC105375675, LRRC2-AS1, and PRKAR2A-AS1 were correlated with age of ASD cases or healthy controls. A significant correlation was detected between expressions of DISC2 and PRKAR2A-AS1. There were inverse correlations between the following pairs of lncRNAs: DISC2/LRRC2-AS1, DISC2/LOC101928237, LRRC2-AS1/PRKAR2A-AS1, LOC101928237/LRRC2-AS1, and LOC101928237 /LOC105375675. We conclude that DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 might be used as potential markers for this condition.

摘要

长链非编码 RNA(lncRNAs)已被认为是神经精神疾病进化中的一个重要的表观遗传因素。我们选择了五个 lncRNAs(DISC2、PRKAR2A-AS1、LOC105375675、LRRC2-AS1 和 LOC101928237)来测量它们在自闭症谱系障碍(ASD)儿童和正常发育儿童的血液样本中的表达。与健康儿童相比,DISC2、PRKAR2A-AS1 和 LOC101928237 在 ASD 病例中的表达增加(后验 Beta=2.508,P 值<0.0001;后验 Beta=2.793,P 值=0.014 和后验 Beta=1.646,P 值<0.0001,分别)。另一方面,与对照组相比,LRRC2-AS1 在 ASD 患者中的表达较低(后验 Beta=-3.781,P 值<0.0001)。值得注意的是,与男孩相比,DISC2 和 PRKAR2A-AS1 在女孩中的表达较低(后验 Beta=-0.982,P 值<0.0001 和后验 Beta=-0.135,P 值<0.0001,分别)。此外,与年龄小于 6 岁的 ASD 病例相比,年龄大于 6 岁的 ASD 病例中 DISC2 的表达较低(后验 Beta=-0.876,P 值=0.003)。DISC2、LOC101928237、LRRC2-AS1 和 PRKAR2A-AS1 在区分 ASD 和健康儿童方面的曲线下面积(AUC)值分别为 0.76、0.90、0.92 和 0.79。DISC2、LOC101928237、LOC105375675、LRRC2-AS1 和 PRKAR2A-AS1 的表达水平均与 ASD 病例或健康对照组的年龄无关。DISC2 和 PRKAR2A-AS1 的表达之间存在显著相关性。lncRNAs 之间存在以下对的反向相关性:DISC2/LRRC2-AS1、DISC2/LOC101928237、LRRC2-AS1/PRKAR2A-AS1、LOC101928237/LRRC2-AS1 和 LOC101928237/LOC105375675。我们得出结论,DISC2、LOC101928237、LRRC2-AS1 和 PRKAR2A-AS1 可能被用作该疾病的潜在标志物。

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