Two genetic variants of CD38 in subjects with autism spectrum disorder and controls
Two genetic variants of CD38 in subjects with autism spectrum disorder and controls
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DOI：
10.1016/j.neures.2010.03.004
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发表时间：
2010-06-01
影响因子：
2.9
通讯作者：
Higashida, Haruhiro
中科院分区：
文献类型：
--
作者：
Munesue, Toshio;Yokoyama, Shigeru;Higashida, Haruhiro
自闭症谱系障碍（ASD）的神经生物学基础仍然知之甚少。鉴于CD38通过催产素（OT）释放在社会识别中的作用，我们假设CD38可能在ASD的病因学中发挥作用。在这里，我们首先检查了CD38的免疫组织化学表达在非ASD受试者死后的大脑下丘脑，发现CD38与OT共定位在分泌神经元。在研究CD38与自闭症之间的关联时，我们通过重新测序主要来自日本病例对照研究的DNA，分析了CD38的10个单核苷酸多态性（SNP）和突变，并且主要招募到自闭症遗传资源交换（AGRE）的高加索病例。在0.6 - 4.6%的日本人群中发现了CD38的SNP，rs6449197（pT）），并且在较小的病例对照研究中与ASD相关。该SNP聚集在T等位基因携带者的父亲和兄弟有ASD或ASD特征的家系中。在该队列中，具有T等位基因的受试者的OT血浆水平低于不具有T等位基因的受试者。一位T等位基因的先证者服用鼻用OT喷雾剂后症状缓解。这两个变异的CD38 poloymorphysms测试可能是感兴趣的ASD的病理生理学方面。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (pT)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.