Polymorphisms of Ionotropic Glutamate Receptor-Related Genes and the Risk of Autism Spectrum Disorder in a Chinese Population

Abstract

Objective: To evaluate the association of GRIK2 and NLGN1 with autism spectrum disorder in a Chinese population.

Methods: We performed spatio-temporal expression analysis of GRIK2 and NLGN1 in the developing prefrontal cortex, and examined the expression of the genes in ASD cases and healthy controls using the GSE38322 data set. Following, we performed a case-control study in a Chinese population.

Results: The analysis using the publicly available expression data showed that GRIK2 and NLGN1 may have a role in the development of human brain and contribute to the risk of ASD. Later genetic analysis in the Chinese population showed that the GRIK2 rs6922753 for the T allele, TC genotype and dominant model played a significant protective role in ASD susceptibility (respectively: OR=0.840, p=0.023; OR=0.802, p=0.038; OR=0.791, p=0.020). The NLGN1 rs9855544 for the G allele and GG genotype played a significant protective role in ASD susceptibility (respectively: OR=0.844, p=0.019; OR=0.717, p=0.022). After adjusting p values, the statistical significance was lost (p>0.05).

Conclusion: Our results suggested that GRIK2 rs6922753 and NLGN1 rs9855544 might not confer susceptibility to ASD in the Chinese population.

Keywords: Autism spectrum disorder; GRIK2; Ionotropic glutamate receptors; NLGN1; Polymorphism.

Figure 1.

Expression patterns of the GRIK2, NLGN1 genes in human frontal cortex. Expression level of the genes across the entire developing stages [from 8 post-conception weeks (pcw) to 40 years (yrs)] were depicted in the frontal cortex, which was divided into DFC, MFC, OFC and VFC. The expression data were downloaded from Brainspan. DFC: dorsolateral prefrontal cortex, VFC: ventrolateral prefrontal cortex, MFC: medial prefrontal cortex, OFC: orbital prefrontal cortex.

Figure 2.

Dysregulation of GRIK2, NLGN1 genes in ASD cases vs cases controls. The vertical axis represented the mRNA expression of NLGN1 and GRIK2 genes in the cerebellum and occipital in GSE38322 data set.