Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism
Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism
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DOI：
10.1038/sj.mp.4001125
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发表时间：
2002-01-01
影响因子：
11
通讯作者：
Insel, TR
中科院分区：
文献类型：
--
作者：
Kim, SJ;Young, LJ;Insel, TR
社会互惠障碍是自闭症的核心组成部分。在临床前研究中，精氨酸加压素（AVP）已被证明通过大脑中的V-1a受体（AVPR 1A）增加一系列社会行为，包括联系和依恋。AVID的行为效应和V1 a受体的神经分布在哺乳动物物种中差异很大。这种区域受体表达的差异以及社会行为的差异可能是由于Via基因（AVPR 1A）5'侧翼区的高度可变重复序列造成的。鉴于这种在社会行为物种间变异中发挥作用的比较证据，我们探索了在我们自己的物种中，人类AVPR 1A的变异是否可能导致社会行为的个体变异，而自闭症代表了社会障碍的一种极端形式。我们对115个自闭症三人组的AVPR 1A 5'侧翼区的两个微卫星多态性进行了基因分型，通过多等位基因传递/不平衡检验（MTDT）发现自闭症与其中一个微卫星标记之间名义上显著的传递不平衡，经Bonferroni校正后不显著。我们还筛选了大约2kb的5'侧翼区和编码区，并确定了10个单核苷酸多态性。
Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V-1a receptor (AVPR1A) in the brain. Both the behavioral effects of AVID and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the Via gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.