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

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.

Common Gene Expression Pattern in the Rat Brain Induced by Several Mood: Stabilizing Drugs / 대한정신약물학회지

OBJECTIVE: This study sought to identify candidate genes related to the clinical effects of several mood stabilizers through gene expression profiles using microarrays and real time RT-PCR. METHOD: Rats were treated with lithium carbonate, valproate, or clozapine for 10 days. Total RNA was extracted from the rat brains and used for microarray analysis. Of 54 genes showing more than 1.5-fold changes induced by all three mood stabilizers, seven genes were selected, and drug-induced changes in gene expression were confirmed by real time RT-PCR. In addition, genotype distribution of the GRIK2 gene was compared between 181 patients with bipolar disorder and 350 normal controls. RESULTS: Of the seven candidate genes, GRIK2 and PRKAR were confirmed as being downregulated by lithium and valproate. However, none of the genes was affected by all three drugs. The allele and genotype distribution in two SNPs of GRIK2 did not differ between the patient and control groups. CONCLUSIONS: Although this study demonstrated overall negative results, the present findings will be used in future studies for establishing various mechanisms of mood stabilizers.