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多巴胺能突触通路基因在注意缺陷多动障碍中的基因相互作用:中国儿童的病例对照研究。

Gene Interaction of Dopaminergic Synaptic Pathway Genes in Attention-Deficit Hyperactivity Disorder: a Case-Control Study in Chinese Children.

机构信息

Medical College of Shihezi University, Xinjiang, Shihezi, 832000, China.

Department of Maternal and Child Health and MOE Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, 430000, China.

出版信息

Mol Neurobiol. 2024 Jan;61(1):42-54. doi: 10.1007/s12035-023-03523-4. Epub 2023 Aug 14.

Abstract

Attention-deficit hyperactivity disorder is a highly inherited neurodevelopmental disorder. Previous genetic research has linked ADHD to certain genes in the dopaminergic synaptic pathway. Nonetheless, research on this relationship has produced varying results across various populations. China is a multi-ethnic country with its own unique genetic characteristics. Therefore, such a population can provide useful information about the relationship between gene polymorphisms in dopaminergic synaptic pathways and ADHD. This study looked at the genetic profiles of 284 children in China's Xinjiang. In total, 142 ADHD children and 142 control subjects were enrolled. Following the extraction of DNA from oral mucosal cells, 13 SNPs for three candidate genes (SLC6A3, DRD2, and GRIN2B) in the dopaminergic synaptic pathway of ADHD were screened. Based on the results of single nucleotide polymorphism (SNP) analyses, we found that the DRD2 gene variants rs6277 and rs6275, and the SLC6A3 gene variant rs2652511, were significantly associated with ADHD in boys and girls, respectively, after adjusting for false discovery rate (FDR) in terms of allele frequencies. Furthermore, our generalized multifactorial downscaling approach identified a significant association between rs6275 and rs1012586. These findings suggest that DRD2 and SLC6A3 genes have a crucial role in ADHD susceptibility. Additionally, we observed that the interaction between GRIN2B and DRD2 genes may contribute to the susceptibility of Chinese children with ADHD.

摘要

注意缺陷多动障碍是一种高度遗传性神经发育障碍。先前的遗传研究将 ADHD 与多巴胺能突触通路中的某些基因联系起来。尽管如此,针对这种相关性的研究在不同人群中产生了不同的结果。中国是一个多民族国家,具有独特的遗传特征。因此,这样的人群可以提供有关多巴胺能突触通路中基因多态性与 ADHD 之间关系的有用信息。本研究关注了中国新疆的 284 名儿童的遗传特征。共有 142 名 ADHD 儿童和 142 名对照受试者被纳入研究。从口腔黏膜细胞中提取 DNA 后,筛选了 ADHD 多巴胺能突触通路中三个候选基因(SLC6A3、DRD2 和 GRIN2B)的 13 个单核苷酸多态性(SNP)。基于单核苷酸多态性(SNP)分析的结果,我们发现,在调整等位基因频率的假发现率(FDR)后,DRD2 基因变体 rs6277 和 rs6275 以及 SLC6A3 基因变体 rs2652511 分别与男孩和女孩的 ADHD 显著相关。此外,我们的广义多因素降尺度方法确定了 rs6275 与 rs1012586 之间的显著关联。这些发现表明,DRD2 和 SLC6A3 基因在 ADHD 易感性中起关键作用。此外,我们观察到 GRIN2B 和 DRD2 基因之间的相互作用可能导致中国 ADHD 儿童易感性的增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ae/10791714/f1bd8e01a167/12035_2023_3523_Fig1_HTML.jpg

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