Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis

Ye, Chuanzhong; Hu, Zhijian; Wu, Eileen; Yang, Xiaolu; Buford, Ushimbra; Guo, Zhihong; Saveanu, Radu V.

doi:10.1016/j.jpsychires.2016.06.007

Cited by 16 publications

(7 citation statements)

References 43 publications

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“…Herken et al ( 2014 ) found that adult patients with the G/G genotype had higher Wender–Utah scores and higher scores in the 1st and 3rd components of the adult ADD/ADHD Scale, and Bidwell et al ( 2017 ) showed a weak correlation between rs3746544 and ADHD in children. Notably, a meta-analysis of subgroups based on race showed that Mnl I polymorphisms were strongly associated with ADHD in Asian populations, but no significant association was identified in Caucasians (Ye et al, 2016 ), indicating that Mnl I polymorphisms are associated with ADHD depending on the genetic background of the population. Moreover, a US study of 165 preschoolers treated with MPH found that G allele carriers were 2–3 times more likely to present with irritability and sleep problems during MPH treatment than T allele carriers (McGough et al, 2006 ), while children with a homozygous T allele (T/T) genotype responded better to MPH treatment.…”

Section: Discussionmentioning

confidence: 99%

Synaptosomal-Associated Protein 25 Gene Polymorphisms Affect Treatment Efficiency of Methylphenidate in Children With Attention-Deficit Hyperactivity Disorder: An fNIRS Study

Yan

et al. 2022

Front. Behav. Neurosci.

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Methylphenidate (MPH) is the first-line drug for the treatment of children with attention-deficit hyperactivity disorder (ADHD); however, individual curative effects of MPH vary. Many studies have demonstrated that synaptosomal-associated protein 25 (SNAP-25) gene MnlI polymorphisms may be related to the efficacy of MPH. However, the association between SNAP-25MnlI polymorphisms and changes in brain hemodynamic responses after MPH treatment is still unclear. This study used functional near-infrared spectroscopy (fNIRS) to preliminarily investigate the interaction of MPH treatment-related prefrontal inhibitory functional changes with the genotype status of the SNAP-25 gene in children with ADHD. In total, 38 children with ADHD aged 6.76–12.08 years were enrolled in this study and divided into the following two groups based on SNAP-25 gene MnlI polymorphisms: T/T genotype group (wild-type group, 27 children) and G allele carrier group (mutation group, 11 children). The averaged oxygenated hemoglobin concentration changes [Δavg oxy-Hb] and deoxyhemoglobin concentration changes [Δavg deoxy-Hb] in the frontal cortex before MPH treatment and after 1.5 h (post-MPH1.5h) and 4 weeks (post-MPH4w) of MPH treatments were monitored using fNIRS during the go/no-go task. SNAP-IV scores were evaluated both pre-MPH and post-MPH4w treatments. In the T/T genotype group, [Δavg oxy-Hb] in the dorsolateral prefrontal cortex was significantly higher after 4 weeks of MPH (post-MPH4W) treatment than pre-treatment; however, in the G allele group, no significant differences in [Δavg oxy-Hb] were observed between pre- and post-treatments. In the go/no-go task, the accuracy was significantly increased post-MPH4w treatment in the T/T genotype group, while no significant differences were observed in response time and accuracy of the “go” sand no-go task in the G allele group for pre-MPH, post-MPH1.5h, and post-MPH4w treatments. The T/T genotype group exhibited a significant decrease in SNAP-IV scores after MPH treatment, while the G allele group showed no significant difference. In conclusion, fNIRS data combined with SNAP-25 MnlI polymorphism analysis may be a useful biomarker for evaluating the effects of MPH in children with ADHD.

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Section: Discussionmentioning

confidence: 99%

Synaptosomal-Associated Protein 25 Gene Polymorphisms Affect Treatment Efficiency of Methylphenidate in Children With Attention-Deficit Hyperactivity Disorder: An fNIRS Study

Yan

et al. 2022

Front. Behav. Neurosci.

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“…Previous studies have indicated that several miRNAs (miR124-1, miR-598, miR-96, miR-18a-5p, miR-22-3p, miR-24-3p, miR-106b-5p, miR-107, miR-155a-5p, and let-7d) may be associated with ADHD ( 32 , 33 , 37 , 38 ). However, none of the aforementioned miRNAs overlapped with those identified in our NGS analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Several explanations may account for this phenomenon. First, the selection of candidate miRNAs in previous studies ( 32 , 33 , 37 , 38 ) relied on underlying neurobiology mechanisms based on literature reviews or the miRNA database. In contrast, we used global screening technology (NGS) to determine the candidate miRNAs, which has a better chance of determining new miRNAs involved in the pathogenesis of ADHD ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Blood-Bourne MicroRNA Biomarker Evaluation in Attention-Deficit/Hyperactivity Disorder of Han Chinese Individuals: An Exploratory Study

Wang

Lee

et al. 2018

Front. Psychiatry

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Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly genetic neurodevelopmental disorder, and its dysregulation of gene expression involves microRNAs (miRNAs). The purpose of this study was to identify potential miRNAs biomarkers and then use these biomarkers to establish a diagnostic panel for ADHD.Design and methods: RNA samples from white blood cells (WBCs) of five ADHD patients and five healthy controls were combined to create one pooled patient library and one control library. We identified 20 candidate miRNAs with the next-generation sequencing (NGS) technique (Illumina). Blood samples were then collected from a Training Set (68 patients and 54 controls) and a Testing Set (20 patients and 20 controls) to identify the expression profiles of these miRNAs with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We used receiver operating characteristic (ROC) curves and the area under the curve (AUC) to evaluate both the specificity and sensitivity of the probability score yielded by the support vector machine (SVM) model.Results: We identified 13 miRNAs as potential ADHD biomarkers. The ΔCt values of these miRNAs in the Training Set were integrated to create a biomarker model using the SVM algorithm, which demonstrated good validity in differentiating ADHD patients from control subjects (sensitivity: 86.8%, specificity: 88.9%, AUC: 0.94, p < 0.001). The results of the blind testing showed that 85% of the subjects in the Testing Set were correctly classified using the SVM model alignment (AUC: 0.91, p < 0.001). The discriminative validity is not influenced by patients' age or gender, indicating both the robustness and the reliability of the SVM classification model.Conclusion: As measured in peripheral blood, miRNA-based biomarkers can aid in the differentiation of ADHD in clinical settings. Additional studies are needed in the future to clarify the ADHD-associated gene functions and biological mechanisms modulated by miRNAs.

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“…SNAP-25 gene has been associated with several human psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Interestingly, postmortem studies on schizophrenia patients’ brains have shown that altered protein levels of SNAP-25 are specific to regions of the brain [ 55 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan

Chen

Alhassen

Monfared

et al. 2021

IJMS

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Almost all brain cells contain primary cilia, antennae-like microtubule sensory organelles, on their surface, which play critical roles in brain functions. During neurodevelopmental stages, cilia are essential for brain formation and maturation. In the adult brain, cilia play vital roles as signaling hubs that receive and transduce various signals and regulate cell-to-cell communications. These distinct roles suggest that cilia functions, and probably structures, change throughout the human lifespan. To further understand the age-dependent changes in cilia roles, we identified and analyzed age-dependent patterns of expression of cilia’s structural and functional components across the human lifespan. We acquired cilia transcriptomic data for 16 brain regions from the BrainSpan Atlas and analyzed the age-dependent expression patterns using a linear regression model by calculating the regression coefficient. We found that 67% of cilia transcripts were differentially expressed genes with age (DEGAs) in at least one brain region. The age-dependent expression was region-specific, with the highest and lowest numbers of DEGAs expressed in the ventrolateral prefrontal cortex and hippocampus, respectively. The majority of cilia DEGAs displayed upregulation with age in most of the brain regions. The transcripts encoding cilia basal body components formed the majority of cilia DEGAs, and adjacent cerebral cortices exhibited large overlapping pairs of cilia DEGAs. Most remarkably, specific α/β-tubulin subunits (TUBA1A, TUBB2A, and TUBB2B) and SNAP-25 exhibited the highest rates of downregulation and upregulation, respectively, across age in almost all brain regions. α/β-tubulins and SNAP-25 expressions are known to be dysregulated in age-related neurodevelopmental and neurodegenerative disorders. Our results support a role for the high dynamics of cilia structural and functional components across the lifespan in the normal physiology of brain circuits. Furthermore, they suggest a crucial role for cilia signaling in the pathophysiological mechanisms of age-related psychiatric/neurological disorders.

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Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis

Cited by 16 publications

References 43 publications

Synaptosomal-Associated Protein 25 Gene Polymorphisms Affect Treatment Efficiency of Methylphenidate in Children With Attention-Deficit Hyperactivity Disorder: An fNIRS Study

Synaptosomal-Associated Protein 25 Gene Polymorphisms Affect Treatment Efficiency of Methylphenidate in Children With Attention-Deficit Hyperactivity Disorder: An fNIRS Study

Blood-Bourne MicroRNA Biomarker Evaluation in Attention-Deficit/Hyperactivity Disorder of Han Chinese Individuals: An Exploratory Study

Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan

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