Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Genes Brain Behav. 2019 Jun;18(5):e12574. doi: 10.1111/gbb.12574. Epub 2019 May 8.
Attention-deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders in children and adolescents with high heritability. Evidence is accumulating that SLC1A3 may play a role in ADHD etiology. Therefore, a two-stage case-control study was conducted on 752 cases and 774 controls to explore the role of SLC1A3 in ADHD. Bioinformatic annotations and functional experiments were applied to reveal the potential biological mechanisms. Finally, SLC1A3 rs1049522 showed significant association with ADHD risk in two stages with CA genotype vs AA genotype, odds ratio (OR) = 0.694 (95% confidence interval, CI = 0.570-0.844) and dominant model, OR = 0.749 (95% CI = 0.621-0.904) in the combined stage. Besides, rs1049522 was found to be related to ADHD hyperactive/impulsive symptom, and rs1049522-C showed increased SLC1A3 mRNA expression in the cerebellar cortex. Dual-luciferase reporter assay further indicated that rs1049522-C allele enhanced SLC1A3 expression by disrupting the hsa-miR-3171 binding site. In conclusion, SLC1A3 variant rs1049522 was implicated in ADHD susceptibility in a Chinese Han population probably by enhancing the SLC1A3 expression in a miRNA-mediated manner.
注意缺陷多动障碍（ADHD）是儿童和青少年中最常见的神经精神疾病之一，具有较高的遗传性。有证据表明 SLC1A3 可能在 ADHD 的发病机制中起作用。因此，我们进行了一项两阶段病例对照研究，共纳入 752 例病例和 774 例对照，以探讨 SLC1A3 在 ADHD 中的作用。我们应用生物信息学注释和功能实验来揭示潜在的生物学机制。最后，SLC1A3 的 rs1049522 与 ADHD 风险显著相关，在两个阶段中 CA 基因型与 AA 基因型相比，比值比（OR）分别为 0.694（95%置信区间，CI=0.570-0.844）和显性模型，OR=0.749（95%CI=0.621-0.904）。此外，rs1049522 与 ADHD 多动/冲动症状有关，rs1049522-C 型等位基因增加小脑皮质中的 SLC1A3 mRNA 表达。双荧光素酶报告基因检测进一步表明，rs1049522-C 等位基因通过破坏 hsa-miR-3171 结合位点增强 SLC1A3 的表达。总之，SLC1A3 变体 rs1049522 可能通过 miRNA 介导的方式增强 SLC1A3 的表达，从而导致中国汉族人群 ADHD 的易感性。
