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中国人群中离子型谷氨酸受体基因变异与注意力缺陷多动障碍的关联:一项两阶段病例对照研究。

Association of Gene Variations in Ionotropic Glutamate Receptor and Attention-Deficit/Hyperactivity Disorder in the Chinese Population: A Two-Stage Case-Control Study.

作者信息

Zhang Qi, Huang Xin, Chen Xin-Zhen, Li Shan-Ya-Wen, Yao Ting, Wu Jing

机构信息

Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

J Atten Disord. 2021 Aug;25(10):1362-1373. doi: 10.1177/1087054720905089. Epub 2020 Feb 17.

Abstract

The aim of this study was to comprehensively explore the relationship between genetic variations within GRIN2A, GRIN2B, GRIK1, GRIK4, GRID2, and ADHD. Genotyping was performed with the Sequenom MassARRAY system in a two-stage case-control study. ADHD symptoms were assessed using the Swanson, Nolan, and Pelham version IV scale and the Integrated Visual and Auditory Continuous Performance Test. In silico analysis was performed with website resources. GRID2 rs1385405 showed a significant association with ADHD risk in the codominant model (OR = 2.208, 95% CI = [1.387, 3.515]) in the first stage and in the codominant model (OR = 1.874, 95% CI = [1.225, 2.869]) and recessive model (OR = 1.906, 95% CI = [1.265, 2.873]) in the second stage and related to inattention and hyperactivity symptom. In addition, rs1385405 disturbed the activity of exonic splicing enhancer and mediated GRID2 gene expression in the frontal cortex. our data provided evidence for the participation of GRID2 variants in conferring the risk of ADHD.

摘要

本研究的目的是全面探究GRIN2A、GRIN2B、GRIK1、GRIK4、GRID2基因内的遗传变异与注意力缺陷多动障碍(ADHD)之间的关系。在一项两阶段病例对照研究中,使用Sequenom MassARRAY系统进行基因分型。使用Swanson、Nolan和Pelham第四版量表以及综合视觉和听觉持续操作测试来评估ADHD症状。利用网站资源进行计算机分析。在第一阶段,GRID2基因的rs1385405在共显性模型中显示出与ADHD风险存在显著关联(比值比[OR]=2.208,95%置信区间[CI]=[1.387, 3.515]);在第二阶段,该位点在共显性模型(OR = 1.874,95% CI = [1.225, 2.869])和隐性模型(OR = 1.906,95% CI = [1.265, 2.873])中与ADHD风险显著相关,且与注意力不集中和多动症状有关。此外,rs1385405破坏了外显子剪接增强子的活性,并介导了额叶皮质中GRID2基因的表达。我们的数据为GRID2基因变异参与ADHD发病风险提供了证据。

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