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