ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin-AVPR1A, AVPR1B, and OXTR.
ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin-AVPR1A, AVPR1B, and OXTR.
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DOI：
10.3389/fnins.2016.00516
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发表时间：
2016
影响因子：
4.3
通讯作者：
Jacob S
中科院分区：
文献类型：
--
作者：
Francis SM;Kim SJ;Kistner-Griffin E;Guter S;Cook EH;Jacob S
背景：自闭症谱系障碍(ASD)的治疗方法有限。已有研究报道催产素(OT)和加压素(AVP)受体基因与ASD诊断以及ASD相关表型之间存在显著的相关性。研究人员还发现，这些系统的操纵会影响社交和重复行为，这是自闭症的核心特征。因此，将催产素/加压素通路作为干预靶点的研究有所增加。因此，对这些神经肽与ASD的关系进行了进一步的研究。在这项研究中，我们研究了加压素(AVPR1A，AVPR1B)、催产素(OXTR)受体基因变异与ASD诊断及相关亚型之间的关系。方法：采用孤独症诊断访谈修订版、孤独症诊断观察表和临床DSM-IV-TR量表对先证者进行评定。对200个有ASD先证者的家系进行了AVPR1B和OXTR的单核苷酸多态(SNPs)和AVPR1A微卫星的基因分型。基于家族的关联测试(FBAT)被用来确定变异与ASD之间的关联。根据先前发表的关联，还分析了由OXTR SNPs(即rs53576-rs2254298-rs2268493)组成的单倍型。结果：应用加性遗传模型，我们发现AVPR1B单核苷酸多态(rs28632197，p=0.005，rs35369693，p=0.025)与诊断有关。与其他研究一样，OXTRrs2268493(p=0.050)与诊断有关。Rs2268493还与社交退缩(p=0.013)和坚持相同(p=0.039)的自闭症亚型相关。进一步分析发现，单倍型rs2254298-rs2268493与诊断显著相关(A-T；p=0.026)。用FBAT对AVPR1A微卫星(RS1和RS3)进行了分析。这两种长度变异都被发现与限制性、重复行为有关，但并不是全部诊断。对每个基因区域检测的SNP进行多重比较校正，只有AVPR1B SNPs与ASD的诊断显著相关。结论：自闭症是一种异质性疾病，有许多促进其发展的基因和途径。OT和AVP受体基因中的SNPs和微卫星与ASD的诊断和社会行为的测量以及限制重复行为有关。我们报道了一种新的与ASD和AVPR1B SNPs相关的基因。了解基因-表型之间的关系可能有助于开发对OT/AVP系统的药物干预。
Background: There are limited treatments available for autism spectrum disorder (ASD). Studies have reported significant associations between the receptor genes of oxytocin (OT) and vasopressin (AVP) and ASD diagnosis, as well as ASD-related phenotypes. Researchers have also found the manipulation of these systems affects social and repetitive behaviors, core characteristics of ASD. Consequently, research involving the oxytocin/vasopressin pathways as intervention targets has increased. Therefore, further examination into the relationship between these neuropeptides and ASD was undertaken. In this study, we examined associations between variants in the receptor genes of vasopressin (AVPR1A, AVPR1B), oxytocin (OXTR), and ASD diagnosis along with related subphenotypes. Methods: Probands were assessed using Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and clinical DSM-IV-TR criteria. Single nucleotide polymorphisms (SNPs) in AVPR1B and OXTR, and microsatellites in AVPR1A were genotyped in ~200 families with a proband with ASD. Family-based association testing (FBAT) was utilized to determine associations between variants and ASD. Haplotypes composed of OXTR SNPs (i.e., rs53576-rs2254298-rs2268493) were also analyzed due to previously published associations. Results: Using the additive inheritance model in FBAT we found associations between AVPR1B SNPs (rs28632197, p = 0.005, rs35369693, p = 0.025) and diagnosis. As in other studies, OXTR rs2268493 (p = 0.050) was associated with diagnosis. rs2268493 was also associated with ASD subphenotypes of social withdrawal (p = 0.013) and Insistence on Sameness (p = 0.039). Further analyses demonstrated that the haplotype, rs2254298–rs2268493 was found to be significantly associated with diagnosis (A-T; p = 0.026). FBAT was also used to analyze AVPR1A microsatellites (RS1 and RS3). Both length variants were found to be associated with restrictive, repetitive behaviors, but not overall diagnosis. Correction for multiple comparisons was performed for SNPs tested in each gene region, only AVPR1B SNPs remained significantly associated with ASD diagnosis. Conclusions: Autism is a heterogeneous disorder with many genes and pathways that contribute to its development. SNPs and microsatellites in the receptor genes of OT and AVP are associated with ASD diagnosis and measures of social behavior as well as restricted repetitive behaviors. We reported a novel association with ASD and AVPR1B SNPs. Understanding of genotype-phenotype relationships may be helpful in the development of pharmacological interventions for the OT/AVP system.
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影响因子：
4.9
作者：
Campbell, Daniel B.;Datta, Dibyadeep;Jones, Shaine T.;Lee, Evon Batey;Sutcliffe, James S.;Hammock, Elizabeth A. D.;Levitt, Pat
通讯作者：
Levitt, Pat
自闭症诊断观察表： 提高诊断有效性的修订算法
影响因子：
3.9
作者：
Gotham, Katherine;Risi, Susan;Lord, Catherine
通讯作者：
Lord, Catherine
影响因子：
4.5
作者：
Davis, Michael C.;Horan, William P.;Nurmi, Erika L.;Rizzo, Shemra;Li, Wendy;Sugar, Catherine A.;Green, Michael F.
通讯作者：
Green, Michael F.
DOI：
10.1111/j.1749-6632.2009.04541.x
发表时间：
2009-01-01
期刊：
VALUES, EMPATHY, AND FAIRNESS ACROSS SOCIAL BARRIERS
影响因子：
--
作者：
Ebstein, Richard P.;Israel, Salomon;Yirmiya, Nurit
通讯作者：
Yirmiya, Nurit
影响因子：
3.5
作者：
Chini, B;Mouillac, B;Barberis, C
通讯作者：
Barberis, C