突触相关蛋白25基因多态性与注意缺陷多动障碍的关联研究

发布时间：2019-01-23 12:45

【摘要】：目的:探索突触体相关蛋白25(SNAP-25)基因多态性与中国儿童注意缺陷多动障碍(ADHD)的关联性,为ADHD的病因学研究提供理论依据。方法:(1)关联性研究:采用病例对照的设计,以到湖南省儿童医院就医的ADHD患儿192名作为病例组,以同期到该院健康体检的192名正常儿童作为对照组。所有研究对象采集2ml静脉血,同时现场询问收集研究对象的人口学特征信息。提取全血DNA,采用Sequenom MassArray系统对SNAP-25基因的rs3746544和rs363006多态性位点进行基因分型。运用SPSS统计软件,采用χ2检验分析病例组与对照组rs3746544和rs363006多态性位点的基因型和等位基因频率有无差别。(2)Meta分析:检索PubMed、Embase、Google Scholar及CNKI数据库内所有SNAP-25与ADHD相关的文献,根据遗传学关联研究报告规范(STREGA)评价文章质量,提取rs3746544和rs363006位点与ADHD关联性研究的数据,运用R软件metafor程序包计算纳入文献的合并统计量OR值及95%置信区间,并绘制森林图,对本研究关联性研究的结果进行验证。此外,对SNAP-25基因的其他多态性位点(rs1051312、rs8636、rs362549、rs362998)与ADHD的关联性做一个全面的Meta分析。结果:(1)关联性研究:多态性位点rs3746544和rs363006在对照组人群中均符合HWE平衡。其中,rs3746544位点等位基因A能显著增加ADHD的发病风险(OR=1.60,95%CI=1.10-2.32,P=0.013),而rs363006位点未与ADHD显示出关联性(OR=0.92,95%CI=0.59-1.42,P=0.692)。(2)Meta分析:rs3746544位点等位基因T(A)能显著增加ADHD的发病风险(OR=1.20,95%CI=1.05-1.37,P=0.008),而rs363006位点未与ADHD显示出关联性(OR=1.02,95%CI=0.86-1.21,P=0.805),与本研究的关联性研究结果一致。SNAP-25其他多态性位点rs10511312、rs8636、rs362549、rs362998与ADHD均无显著关联性。结论:本次关联性研究发现SNAP-25基因多态位点rs3746544与ADHD的发病存在有统计学意义的关联,Meta分析同样支持该关联,但这种关联性还需要后续的功能学研究验证。
[Abstract]:Objective: to explore the association of synaptosomal associated protein 25 (SNAP-25) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in Chinese children and to provide a theoretical basis for the etiological study of ADHD. Methods: (1) correlation study: using a case-control design, 192 children with ADHD in Hunan Children's Hospital were selected as case group and 192 normal children as control group. 2ml venous blood was collected from all subjects, and demographic characteristics of the subjects were collected at the same time. Whole blood DNA, was extracted and genotyped by Sequenom MassArray system for rs3746544 and rs363006 polymorphism of SNAP-25 gene. Using SPSS statistical software, 蠂 2 test was used to analyze the difference of genotype and allele frequency of rs3746544 and rs363006 polymorphism loci between case group and control group. (2) Meta analysis: search PubMed,Embase, All SNAP-25 and ADHD related literature in Google Scholar and CNKI databases were evaluated according to the genetic association study report (STREGA) was used to evaluate the quality of the article, and the data of rs3746544 and rs363006 loci were extracted from ADHD correlation study. The combined statistical OR value and 95% confidence interval were calculated by using R software metafor package, and the forest map was drawn to verify the results of this study. In addition, a comprehensive Meta analysis of the association between other polymorphic loci (rs1051312,rs8636,rs362549,rs362998) of SNAP-25 gene and ADHD was made. Results: (1) Association study: polymorphism locus rs3746544 and rs363006 all accord with HWE balance in control group. The allele A of rs3746544 locus significantly increased the risk of ADHD (OR=1.60,95%CI=1.10-2.32,P=0.013), while the rs363006 locus was not correlated with ADHD (OR=0.92,95%CI=0.59-1.42,). Meta analysis of P0. 692). (2: rs3746544 allele T (A) could significantly increase the risk of ADHD (OR=1.20,95%CI=1.05-1.37,P=0.008). However, rs363006 locus showed no association with ADHD (OR=1.02,95%CI=0.86-1.21,P=0.805), which was consistent with the results of this study. There was no significant correlation between rs10511312,rs8636,rs362549,rs362998 and ADHD at other polymorphic SNAP-25 loci. Conclusion: this association study found that there was a statistically significant association between the polymorphic locus rs3746544 of SNAP-25 gene and the pathogenesis of ADHD, which was supported by Meta analysis, but this association needs to be verified by further functional studies.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.94

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