Association study between inwardly rectifying potassium channels 2.1 and 4.1 and autism spectrum disorders
Association study between inwardly rectifying potassium channels 2.1 and 4.1 and autism spectrum disorders
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内向整流钾通道2.1和4.1与自闭症谱系障碍的关联研究
DOI：
10.1016/j.lfs.2018.10.012
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发表时间：
2018-11
期刊：
影响因子：
6.1
通讯作者：
Huan Ren
中科院分区：
文献类型：
--
作者：
Caihong Sun;Mingyang Zou;Ling Li;Dexin Li;Yongjuan Ma;Wei Xia;Lijie Wu;Huan Ren
自闭症谱系障碍（ASD）是一组涉及大脑结构和功能障碍的神经发育障碍。抑制整流钾（Kir）通道可能通过改变脑功能而导致ASD的病因。本研究探讨了KCNJ 2和KCNJ 10基因（分别编码Kir2.1和Kir4.1）的遗传变异与患者ASD风险之间的关系，以及ASD模型大鼠中Kir通道的表达。这项病例对照研究包括269名中国ASD儿童和243名无关的健康对照。采用Sequenom Mass Array对KCNJ 2和KCNJ 10基因的12个标签单核苷酸多态性（SNP）进行基因分型，同时采用丙戊酸（VPA）诱导的ASD大鼠模型评价海马Kir通道的表达。在检测的12个SNPs中，只有KCNJ 10 rs 1186689与疾病易感性显著相关; T等位基因变异可降低ASD的发病风险[比值比（OR）= 0.61，95%CI = 0.47- 0.80，p假发现率（FDR）= 0.012，OR = 0.63，95%CI = 0.48-0.84，分别在等位基因和基因型水平上pFDR= 0.014]。此外，与对照组大鼠相比，VPA组海马Kir2.1和Kir4.1水平降低。结果表明KCNJ 10（rs 1186689）基因多态性与中国汉族儿童ASD易感性相关，在ASD模型大鼠中Kir2.1和Kir4.1的异常表达提示Kir通道可能参与了ASD的发病机制。
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders involving structural and functional impairment of the brain. Inwardly rectifying potassium (Kir) channels may contribute to the etiology of ASD by altering brain function. This study investigated the associations between genetic variants ofKCNJ2and KCNJ10 genes (encoding Kir2.1 and Kir4.1, respectively) and ASD risk in patients, and Kir channel expression in ASD model rats. This case-control study involved a cohort of 269 Chinese children with ASD and 243 unrelated healthy controls. Twelve tag single nucleotide polymorphisms (SNPs) from theKCNJ2andKCNJ10genes were genotyped by Sequenom Mass Array, while a valproic acid (VPA)-induced rat model of ASD was used to evaluate Kir channel expression in the hippocampus. Among the 12 examined SNPs, onlyKCNJ10 rs1186689was significantly associated with disease susceptibility; the variant T allele conferred a lower risk of developing ASD [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47–0.80,pfalse discovery rate (FDR) = 0.012, and OR = 0.63, 95% CI = 0.48–0.84,pFDR= 0.014 at the allelic and genotypic levels, respectively]. Additionally, hippocampal Kir2.1 and Kir4.1 levels were decreased in VPA as compared to control rats. These results demonstrated thatKCNJ10(rs1186689) polymorphisms was correlated with ASD susceptibility in Chinese Han children, and the abnormal expression of Kir2.1 and Kir4.1 in ASD model rats suggested a mechanism by which Kir channels may play a role in ASD.
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
Benjamin Zablotsky;Lindsey I. Black;M. Maenner;L. Schieve;S. Blumberg
通讯作者：
Benjamin Zablotsky;Lindsey I. Black;M. Maenner;L. Schieve;S. Blumberg
影响因子：
3.7
作者：
Imbrici P;Camerino DC;Tricarico D
通讯作者：
Tricarico D