Peking University Sixth Hospital/Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Peking University Sixth Hospital/Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:132-9. doi: 10.1016/j.pnpbp.2014.11.001. Epub 2014 Nov 13.
N-ethylmaleimide-sensitive attachment protein receptor (SNARE) complex involved in neurotransmission via exocytosis was implicated in attention-deficit/hyperactivity disorder (ADHD). The present study investigated the influence of SNARE related genes and their interaction on ADHD susceptibility and their cognitive functions.
We genotyped eight single nucleotide polymorphisms (SNP) of Syntaxin 1A (STX1A), vesicle-associated membrane protein 2 (VAMP2) and synaptosomal-associated protein 25 kDa (SNAP25) and conducted case-control studies in 1404 male ADHD and 617 male controls. Quantitative analyses were performed for genotypes and performance on the Rey-Osterrieth complex figure test (RCFT), digit span test and Stroop test in 383 ADHD males. In addition, we explored gene-gene interactions by generalized multifactor dimensionality reduction (GMDR) followed with logistic regression and analyses of covariance for verifying.
Genotypic distribution of rs875342 of STX1A was significantly different between ADHD and controls. The SNPs, rs363039 of SNAP25 and rs1150 of VAMP2, were significantly associated with RCFT scores, while rs875342 of STX1A with digit span. We found genetic interaction models between these three genes and ADHD susceptibility as well as working memory function evaluated by RCFT.
SNARE complex genes and their interactions may play a significant role in susceptibility and working memory of ADHD.
参与通过胞吐作用进行神经传递的 N-乙基马来酰亚胺敏感的附着蛋白受体（SNARE）复合物与注意力缺陷多动障碍（ADHD）有关。本研究调查了 SNARE 相关基因及其相互作用对 ADHD 易感性及其认知功能的影响。
我们对 Syntaxin 1A（STX1A）、囊泡相关膜蛋白 2（VAMP2）和突触相关蛋白 25kDa（SNAP25）的 8 个单核苷酸多态性（SNP）进行了基因分型，并在 1404 名男性 ADHD 和 617 名男性对照中进行了病例对照研究。对 383 名 ADHD 男性的基因型和 Rey-Osterrieth 复杂图形测试（RCFT）、数字跨度测试和 Stroop 测试的表现进行了定量分析。此外，我们通过广义多因子降维（GMDR）进行了基因-基因相互作用的探索，随后进行了逻辑回归和协方差分析以进行验证。
STX1A 的 rs875342 基因型分布在 ADHD 和对照组之间存在显著差异。SNAP25 的 rs363039 和 VAMP2 的 rs1150 与 RCFT 评分显著相关，而 STX1A 的 rs875342 与数字跨度相关。我们发现这三个基因与 ADHD 易感性以及 RCFT 评估的工作记忆之间存在遗传相互作用模型。
SNARE 复合物基因及其相互作用可能在 ADHD 的易感性和工作记忆中发挥重要作用。
