SNAP-25、STX1A基因多态性与小儿注意缺陷多动障碍易感性的关系及交互作用分析-现代医学

SNAP-25、STX1A基因多态性与小儿注意缺陷多动障碍易感性的关系及交互作用分析

作者：郑芳国志

单位：上海交通大学医学院附属第六人民医院儿科, 上海 201306

关键词：小儿注意缺陷多动障碍突触关联蛋白-25 突触融合蛋白-1A 基因多态性易感性交互作用

分类号：R748

出版年·卷·期（页码）：2023·51·第一期（24-31）

摘要：

目的: 探究突触关联蛋白-25(SNAP-25)、突触融合蛋白-1A(STX1A)基因多态性与小儿注意缺陷多动障碍(ADHD)易感性的关系及交互作用。方法: 将我院2020年6月到2022年4月门诊就诊的98例ADHD患儿纳入观察组，同期健康体检儿童65例作为对照组。采集研究对象外周静脉血3 ml，采用聚合酶链式反应(PCR)-限制性片段长度多态性法(RFLP)对SNAP-25基因位点(rs3746544)、STX1A基因位点(rs2228607、rs875342)进行分型，比较两组研究对象一般资料、ADHD筛查量表(SNAP-IV)评分、SNAP-25与STX1A基因型及等位基因分布，采用二元Logistic回归模型分析SNAP-25、STX1A基因多态性与ADHD易感性的关联性及交互作用。结果: 观察组患儿SNAP-IV中的注意缺陷、多动/冲动评分及平均分均高于对照组(P<0.05)；SNAP-2 rs3746544位点携带T/T基因型的儿童多动/冲动评分及平均分均高于G/G、G/T基因型儿童(P<0.05)，STX1A rs2228607与rs875342位点携带A/A基因型的儿童注意缺陷评分及平均分均高于G/G、A/G基因型儿童(P<0.05)；SNAP-25 rs3746544位点上携带T等位基因及STX1A rs2228607、rs875342位点上携带A等位基因可增加小儿ADHD患病风险(P<0.05)；交互携带rs3746544位点 GT/TT基因型、rs2228607与rs875342位点 GA/AA基因型的小儿ADHD患病风险高于交互携带GG基因型者(P<0.05)。结论: SNAP-25 rs3746544位点与STX1A rs2228607、rs875342位点的突变基因均可增加小儿ADHD易感性，且两基因及不同位点间存在交互作用，共同参与ADHD的发生、发展过程。

Objective: To explore the relationship between gene polymorphisms of synaptosomal-associated protein of 25 kda(SNAP-25) and syntaxin-1A(STX1A) and susceptibility of children with attention deficit hyperactivity disorder(ADHD) and analyze their interaction effects.Methods: 98 children with ADHD seen in the outpatient clinic from June 2020 to April 2022 were included in the observation group, and 65 healthy children undergoing physical examination in the hospital during the same period were enrolled as the control group. 3 ml of peripheral venous blood was collected from the research subjects, and the SNAP-25 gene loci(rs3746544) and STX1A gene loci(rs2228607, rs875342) were genotyped by polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP). General data, Swanson,Nolan and Pelham-IV rating scale(SNAP-IV) scores and distribution of genotypes and alleles of SNAP-25 and STX1A were compared between the two groups. Binary Logistic regression model was used to analyze the association and interaction effects between gene polymorphisms of SNAP-25 and STX1A and ADHD susceptibility.Results: The scores of attention deficit and hyperactivity/impulsivity and average score of SNAP-IV in the observation group were higher than those in the control group(P<0.05). The hyperactivity/impulsivity score and average score of children carrying T/T genotype at rs3746544 locus of SNAP-2 gene were higher compared with those of children carrying G/G genotype or G/T genotype(P<0.05). The attention deficit score and average score of children carrying A/A genotype at rs2228607 and rs875342 loci of STX1A gene were higher than those of children carrying G/G and A/G genotypes(P<0.05). T allele at SNAP-25 rs3746544 locus and A allele at STX1A rs2228607 and rs875342 locus could increase the risk of ADHD in children(P<0.05). The risk of ADHD in children with GT/TT genotype of rs3746544 locus, GA/AA genotype of rs2228607 and rs875342 locus was higher than that in children with GG genotype(P<0.05).Conclusion: Both SNAP-25 and STX1A are ADHD susceptibility genes. Mutant genes at SNAP-25 rs3746544 locus and STX1A rs3746544 and rs875342 loci can increase the risk of ADHD in children, and there is an interaction effect between the different loci SNAP-25 gene and STX1A gene, and the two genes jointly participate in the occurrence and development of ADHD.

参考文献：

[1] CHEN X,YAO T,CAI J,et al.A novel genetic variant potentially altering the expression of MANBA in the cerebellum associated with attention deficit hyperactivity disorder in Han Chinese children[J].World J Biol Psychiatry,2022,13(1):1-12.
[2] AGNEW-BLAIS J C,BELSKY D W,CASPI A,et al.Polygenic risk and the course of attention-deficit/hyperactivity disorder from childhood to young adulthood:findings from a nationally representative cohort[J].J Am Acad Child Adolesc Psychiatry,2021,60(9):1147-1156.
[3] 丁凯景，丁雨钦，周圆月，等.GRIN2A、GRIN2B基因多态性与注意缺陷多动障碍的关联研究[J].浙江医学，2021，43(10)：1066-1070.
[4] BOLAT H,ÜNSEL-BOLAT G,ÖZGÜL S,et al.Investigation of possible associations of the BDNF,SNAP-25 and SYN Ⅲ genes with the neurocognitive measures:BDNF and SNAP-25 genes might be involved in attention domain,SYN Ⅲ gene in executive function[J].Nord J Psychiatry,2022,25(1):1-6.
[5] CUPERTINO R B,SCHUCH J B,BANDEIRA C E,et al.Replicated association of Synaptotagmin(SYT1) with ADHD and its broader influence in externalizing behaviors[J].Eur Neuropsychopharmacol,2017,27(3):239-247.
[6] CERVANTES-HENRIQUEZ M L,ACOSTA-LÓPEZ J E,MARTINEZ A F,et al.Machine learning prediction of ADHD severity:association and linkage to ADGRL3,DRD4,and SNAP25[J].J Atten Disord,2022,26(4):587-605.
[7] HANĆT,DMITRZAK-WEGLARZ M,BORKOWSKA A,et al.Overweight in boys with ADHD is related to candidate genes and not to deficits in cognitive functions[J].J Atten Disord,2018,22(12):1158-1172.
[8] PUENTES-ROZO P J,ACOSTA-LÓPEZ J E,CERVANTES-HENRIQUEZ M L,et al.Genetic variation underpinning ADHD risk in a caribbean community[J].Cells,2019,8(8):907-910.
[9] 刘寰忠，钟怡.2018版加拿大儿科学会《儿童青少年注意缺陷多动障碍诊疗指南》解读[J].中国全科医学，2019，22(14)：1641-1647.
[10] 中华医学会儿科学分会发育行为学组.注意缺陷多动障碍早期识别、规范诊断和治疗的儿科专家共识[J].中华儿科杂志，2020，58(3)：188-193.
[11] 李皓.韦克斯勒儿童智力测验量表第3版(WISC-Ⅲ)简介[J].中国学校卫生，2006，27(3)：247-248.
[12] QI X,WANG S,ZHANG L,et al.An integrative analysis of transcriptome-wide association study and mRNA expression profile identified candidate genes for attention-deficit/hyperactivity disorder[J].Psychiatry Res,2019,282(1):112639-112642.
[13] TIAN T,ZHANG Y,WU T,et al.miRNA profiling in the hippocampus of attention-deficit/hyperactivity disorder rats[J].J Cell Biochem,2019,120(3):3621-3629.
[14] 伍毅，吴贻明，宋兵福，等.中国汉族人群SNAP25基因多态性与精神分裂症的关联研究[J].上海交通大学学报(医学版)，2019，39(10)：1172-1177.
[15] LIU Y S,DAI X,WU W,et al.The association of SNAP25 gene polymorphisms in attention deficit/hyperactivity disorder:a systematic review and meta-analysis[J].Mol Neurobiol,2017,54(3):2189-2200.
[16] LEO D,SUKHANOV I,ZORATTO F,et al.Pronounced hyperactivity,cognitive dysfunctions,and BDNF dysregulation in dopamine transporter knock-out rats[J].J Neurosci,2018,38(8):1959-1972.
[17] WANG C,YANG B,FANG D,et al.The impact of SNAP25 on brain functional connectivity density and working memory in ADHD[J].Biol Psychol,2018,138(1):35-40.
[18] KIM E,SONG D H,KIM N W,et al.The relationship between the SNAP-25 polymorphism and omission errors in korean children with attention deficit hyperactivity disorder[J].Clin Psychopharmacol Neurosci,2017,15(3):222-228.
[19] LI J,YAN W J,WU Y,et al.Synaptosomal-associated protein 25 gene polymorphisms affect treatment efficiency of methylphenidate in children with attention-deficit hyperactivity disorder:an fNIRS study[J].Front Behav Neurosci,2022,15(1):793643-793645.
[20] FANG D,YANG B,WANG P,et al.Role of SNAP-25 MnlI variant in impaired working memory and brain functions in attention deficit/hyperactivity disorder[J].Brain Behav,2022,12(10):e2758.
[21] YANG H,ZHANG M,SHI J,et al.Brain-specific SNAP-25 deletion leads to elevated extracellular glutamate level and schizophrenia-like behavior in mice[J].Neural Plast,2017,2017(1):452641-452647.
[22] WANG M,GU X,HUANG X,et al.STX1A gene variations contribute to the susceptibility of children attention-deficit/hyperactivity disorder:a case-control association study[J].Eur Arch Psychiatry Clin Neurosci,2019,269(6):689-699.
[23] HIRAOKA Y,SUGIYAMA K,NAGAOKA D,et al.Mice with reduced glutamate transporter GLT1 expression exhibit behaviors related to attention-deficit/hyperactivity disorder[J].Biochem Biophys Res Commun,2021,567(1):161-165.
[24] BIDWELL L C,GRAY J C,WEAFER J,et al.Genetic influences on ADHD symptom dimensions:examination of a priori candidates,gene-based tests,genome-wide variation,and SNP heritability[J].Am J Med Genet B Neuropsychiatr Genet,2017,174(4):458-466.
[25] ZHANG S,YOU L,XU Q,et al.Distinct long non-coding RNA and mRNA expression profiles in the hippocampus of an attention deficit hyperactivity disorder model in spontaneously hypertensive rats and control wistar Kyoto rats[J].Brain Res Bull,2020,161(1):177-196.
[26] KARMAKAR S,SHARMA L G,ROY A,et al.Neuronal SNARE complex:a protein folding system with intricate protein-protein interactions,and its common neuropathological hallmark,SNAP25[J].Neurochem Int,2019,122(1):196-207.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录