Family-based clinical associations and functional characterization of the serotonin 2A receptor gene (HTR2A) in autism spectrum disorder.
Family-based clinical associations and functional characterization of the serotonin 2A receptor gene (HTR2A) in autism spectrum disorder.
复制标题
自闭症谱系障碍中血清素 2A 受体基因 (HTR2A) 的基于家庭的临床关联和功能特征。
DOI：
10.1002/aur.1383
复制
发表时间：
2014-08
期刊：
影响因子：
4.7
通讯作者：
Herman, Gail E.
中科院分区：
文献类型：
--
作者：
Smith, Ryan M.;Banks, Wesley;Hansen, Emily;Sadee, Wolfgang;Herman, Gail E.
5-羟色胺2A受体基因（HTR 2A）具有两种在非洲和欧洲血统人群中常见的功能性单核苷酸多态性（SNP）; rs6311，影响mRNA表达，rs6314，改变编码蛋白质的氨基酸序列并影响受体的信号传导特性。尽管自闭症谱系障碍（ASD）的研究仍然模棱两可，但多个临床关联支持这些SNP在认知和神经精神表型中的作用。在这里，我们测试了rs6311和rs6314在158个ASD三重（单纯和多重）队列中的传递不平衡，观察到rs6311的次要“A”等位基因向ASD后代的显著传递不足（排列p=0.0004）。与我们之前在未受影响个体的背外侧前额叶皮层中的发现一致，rs6311/A降低了54名ASD患者和对照组大脑样本中额极皮层HTR 2A mRNA的表达，并延长了5′非翻译区。在我们的mRNA表达分析的背景下解释临床结果，我们推测与rs6311相关的任何风险都是由长5′UTR mRNA亚型的更高表达所赋予的。目前的研究证实了家族研究中rs6311与ASD之间的早期关联，支持rs6311在ASD风险中起调节作用的假设。
The serotonin 2A receptor gene (HTR2A) harbors two functional single nucleotide polymorphisms (SNPs) that are frequent in populations of African and European descent; rs6311, which affects mRNA expression, and rs6314, which changes the amino acid sequence of the encoded protein and affects the signaling properties of the receptor. Multiple clinical associations support a role for these SNPs in cognitive and neuropsychiatric phenotypes, although studies in autism spectrum disorder (ASD) remain equivocal. Here, we tested transmission disequilibrium of rs6311 and rs6314 in a cohort of 158 ASD trios (simplex and multiplex), observing significant under-transmission of the minor “A” allele of rs6311 to offspring with ASD (permuted p=0.0004). Consistent with our previous findings in the dorsolateral prefrontal cortex of unaffected individuals, rs6311/A decreases expression of HTR2A mRNA with an extended 5′ untranslated region in the frontopolar cortex in brain samples from 54 ASD patients and controls. Interpreting the clinical results in the context of our mRNA expression analysis, we speculate that any risk associated with rs6311 is conferred by greater expression of the long 5′UTR mRNA isoform. The current study corroborates earlier associations between rs6311 and ASD in a family study, supporting the hypothesis that rs6311 plays a modulatory role in ASD risk.
登录
查看更多内容
影响因子：
4.7
作者：
Cottrell, Catherine E.;Bir, Natalie;Varga, Elizabeth;Alvarez, Carlos E.;Bouyain, Samuel;Zernzach, Randall;Thrush, Devon L.;Evans, Johnna;Trimarchi, Michael;Butter, Eric M.;Cunningham, David;Gastier-Foster, Julie M.;McBride, Kim L.;Herman, Gail E.
通讯作者：
Herman, Gail E.
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：
11
作者：
Kato, M.;Serretti, A.
通讯作者：
Serretti, A.
影响因子：
3.6
作者：
Cook, Edwin H., Jr.;Leventhal, Bennett L.
通讯作者：
Leventhal, Bennett L.
DOI：
10.1073/pnas.95.2.735
发表时间：
1998-01-20
影响因子：
11.1
作者：
Jakab, RL;Goldman-Rakic, PS
通讯作者：
Goldman-Rakic, PS