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在印度东部注意缺陷多动障碍先证者中探索 SNAP25 的作用。

Role of SNAP25 explored in eastern Indian attention deficit hyperactivity disorder probands.

机构信息

Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.

出版信息

Neurochem Res. 2012 Feb;37(2):349-57. doi: 10.1007/s11064-011-0618-8. Epub 2011 Oct 14.

Abstract

Synaptosomal-associated protein 25 (SNAP25) is an essential component for synaptic vesicle mediated release of neurotransmitters. Deficiencies or abnormal structure or function of SNAP25 protein, possibly arising through genetic variations in the relevant DNA code, has been suggested to play role in the pathology of several neurobehavioural disorders including Attention deficit Hyperactivity Disorder (ADHD) and a number of polymorphisms in the SNAP25 gene has been studied for association with the disorder. In the present investigation, for the first time association between ADHD and six SNAP25 polymorphisms, rs1889189, rs362569, rs362988, rs3746544, rs1051312, and rs8636 was explored in eastern Indian population. Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Genomic DNA isolated from peripheral blood leukocytes of ADHD probands (n = 150), their parents (n = 272) and ethnically matched controls (n = 100) was used for amplifying target sites. Data obtained were subjected to population- as well as family-based analyses. While case-control analysis revealed lack of any significant difference for alleles, family-based studies revealed a mild over transmission rs3746544 'T' and rs8636 'C' alleles (P = 0.05 and 0.03 respectively). Haplotypes formed between rs362569 "T", 362988 "G", rs3746544 "T", rs1051312 "T" and rs8636 "C" in different combinations showed statistically significant transmission to ADHD probands. Excepting rs3746544 and rs8636, all the tested sites showed very low linkage disequilibrium between them. Data obtained in this preliminary study indicates that rs3746544 'T' allele may have some role in the disease etiology in the studied Indian population.

摘要

突触相关蛋白 25(SNAP25)是介导神经递质突触囊泡释放的必需成分。SNAP25 蛋白的缺乏或结构或功能异常,可能是由于相关 DNA 编码中的遗传变异引起的,被认为在包括注意力缺陷多动障碍(ADHD)在内的几种神经行为障碍的发病机制中起作用,并且已经研究了 SNAP25 基因的许多多态性与该疾病的关联。在本研究中,首次在印度东部人群中研究了 ADHD 与六个 SNAP25 多态性(rs1889189、rs362569、rs362988、rs3746544、rs1051312 和 rs8636)之间的关联。按照《精神障碍诊断与统计手册》第 IV 版,对 ADHD 先证者(n=150)、其父母(n=272)和种族匹配的对照者(n=100)的外周血白细胞中分离的基因组 DNA 进行扩增。对获得的数据进行群体和基于家庭的分析。虽然病例对照分析显示等位基因没有任何显著差异,但基于家庭的研究显示 rs3746544“T”和 rs8636“C”等位基因的轻度过度传递(分别为 P=0.05 和 0.03)。在不同组合中形成的 rs362569“T”、362988“G”、rs3746544“T”、rs1051312“T”和 rs8636“C”之间的单体型与 ADHD 先证者有统计学意义的传递。除了 rs3746544 和 rs8636 之外,所有测试的位点之间都显示出非常低的连锁不平衡。这项初步研究的数据表明,rs3746544“T”等位基因可能在研究人群中的疾病病因中起一定作用。

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