电压门控钾通道Kv2.1和Kv4.2基因多态性与自闭症谱系障碍易感性之间的关联。

The association between gene polymorphisms in voltage-gated potassium channels Kv2.1 and Kv4.2 and susceptibility to autism spectrum disorder.

作者信息

Liu Zehui, Yang Xiaolei, Guo Peiwen, Wang Feng, Xia Wei, Chen Yuxin, Zou Mingyang, Sun Caihong

机构信息

Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, China.

Department of Preventive Medicine, School of Public Health, Qiqihar Medical University, Qiqihar, China.

出版信息

Front Psychiatry. 2023 Jan 23;13:994166. doi: 10.3389/fpsyt.2022.994166. eCollection 2022.

DOI:10.3389/fpsyt.2022.994166

PMID:36756634

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9900626/

Abstract

BACKGROUND

Autism spectrum disorder (ASD) is a heritable form of neurodevelopmental disorder that arises through synaptic dysfunction. Given the involvement of voltage-gated potassium (Kv) channels in the regulation of synaptic plasticity, we aimed to explore the relationship between the genetic variants in the and genes (encoding Kv2.1 and Kv4.2, respectively) and the risk of developing ASD.

METHODS

A total of 243 patients with ASD and 243 healthy controls were included in the present study. Sixty single nucleotide polymorphisms (SNPs) (35 in and 25 in ) were genotyped using the Sequenom Mass Array.

RESULTS

There were no significant differences in the distribution of allele frequencies and genotype frequencies in between cases and controls. However, the differences were significant in the allelic distribution of ( < 0.005) and ( < 0.005) between the two groups. ( = 0.045) in the dominant model and ( < 0.001) and ( < 0.001) in the over-dominant model were associated with ASD risk. The G/A genotype of in the over-dominant model and the G/A-G/G genotype of in the dominant model were correlated with lower severity in the Autism Diagnostic Interview-Revised (ADI-R) restricted repetitive behavior (RRB) domain.

CONCLUSION

Our results provide evidence that gene polymorphism is strongly associated with ASD susceptibility and the severity of RRB.

摘要

背景

自闭症谱系障碍（ASD）是一种通过突触功能障碍产生的遗传性神经发育障碍。鉴于电压门控钾（Kv）通道参与突触可塑性的调节，我们旨在探讨KCNB1和KCND2基因（分别编码Kv2.1和Kv4.2）中的基因变异与患ASD风险之间的关系。

方法

本研究共纳入243例ASD患者和243名健康对照。使用Sequenom Mass Array对60个单核苷酸多态性（SNP）（KCNB1中35个，KCND2中25个）进行基因分型。

结果

病例组和对照组之间KCNB1等位基因频率和基因型频率的分布没有显著差异。然而，两组之间KCND2的等位基因分布差异显著（P<0.005）。显性模型中的rs2229881（P=0.045）以及超显性模型中的rs2229881（P<0.001）和rs17465783（P<0.001）与ASD风险相关。超显性模型中KCND2的G/A基因型以及显性模型中KCND2的G/A - G/G基因型与自闭症诊断访谈修订版（ADI - R）受限重复行为（RRB）领域的较低严重程度相关。