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

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

JOURNAL=Frontiers in Psychiatry

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.994166

DOI=10.3389/fpsyt.2022.994166

ISSN=1664-0640

ABSTRACT=<sec><title>Background</title><p>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 <italic>KCNB1</italic> and <italic>KCND2</italic> genes (encoding Kv2.1 and Kv4.2, respectively) and the risk of developing ASD.</p></sec><sec><title>Methods</title><p>A total of 243 patients with ASD and 243 healthy controls were included in the present study. Sixty single nucleotide polymorphisms (SNPs) (35 in <italic>KCNB1</italic> and 25 in <italic>KCND2</italic>) were genotyped using the Sequenom Mass Array.</p></sec><sec><title>Results</title><p>There were no significant differences in the distribution of allele frequencies and genotype frequencies in <italic>KCNB1</italic> between cases and controls. However, the differences were significant in the allelic distribution of <italic>KCND2 rs1990429</italic> (<italic>p</italic><sub><italic>Bonferroni</italic></sub> &lt; 0.005) and <italic>rs7793864</italic> (<italic>p</italic><sub><italic>Bonferroni</italic></sub> &lt; 0.005) between the two groups. <italic>KCND2 rs7800545</italic> (<italic>p</italic><sub><italic>FDR</italic></sub> = 0.045) in the dominant model and <italic>rs1990429</italic> (<italic>p</italic><sub><italic>FDR</italic></sub> &lt; 0.001) and <italic>rs7793864</italic> (<italic>p</italic><sub><italic>FDR</italic></sub> &lt; 0.001) in the over-dominant model were associated with ASD risk. The G/A genotype of <italic>rs1990429</italic> in the over-dominant model and the G/A–G/G genotype of <italic>rs7800545</italic> in the dominant model were correlated with lower severity in the Autism Diagnostic Interview-Revised (ADI–R) restricted repetitive behavior (RRB) domain.</p></sec><sec><title>Conclusion</title><p>Our results provide evidence that <italic>KCND2</italic> gene polymorphism is strongly associated with ASD susceptibility and the severity of RRB.</p></sec>