Aberrant glutamate signaling leads to excitatory/inhibitory imbalance which is associated with the development of ASD [7, 26, 27]. This study examined SNPs in genes related to the glutamate signaling pathway and analyzed their relationships with the risk of ASD and its severity in a Chinese Han population. Our results revealed that only SNP rs2292813 in the SLC25A2 gene, but not the other SNPs, was associated with ASD. None of the SNPs examined was associated with disease severity.
A Finnish case-control study genotyped rs2228622, rs12682807, rs2072657, rs301430, rs1471786 and rs301979 of the SLC1A1 gene in 175 patients with ASD and 216 controls. Similar to our study, no association was found between these SNPs and ASD . Another family-based study examined rs301430, rs301979 and rs301434 in 86 strictly defined trios. Their result revealed that the G allele of rs301979 and haplotype T-G of rs301430 -rs301979 were undertransmitted to individuals with ASD, although this was not evident after correction for multiple comparisons . These results suggest that these SNPs in the SLC1A1 gene are not biomarkers for ASD.
SLC25A12 has been considered a candidate gene for the development of ASD [11, 12]. Several studies conducted one decade ago reported an association between ASD and SNPs rs2292813, rs2056202 [30–32] and rs908670  in the SLC25A12 gene, though a few others found no association between ASD and these SNPs [34, 35], including one study conducted within a Han population in Taiwan . Two Recent meta-analyses, including one from our group, summarized studies published before 2014 and both concluded a strong association between SNPs rs2056202 and rs2292813 and ASD [20, 36]. With a smaller sample size, we have previously demonstrated a positive association with rs2056202 and rs2292813 and the risk of ASD . Findings in this study present further supportive evidence that SNP rs2292813 is associated with the risk of ASD.
Although findings from this study didn’t reveal a significant association between SNPs of the GMR7 gene and childhood ASD, at least two separate groups did demonstrate a significant correlation. Yang et al  utilized Affymetrix Genome-Wide Human SNP microarrays to analyze 297 SNPs in the GRM7 gene in 22 patients with ASD, 14 non-ASD patients, and 18 healthy controls from a Chinese Han population. Their study found that genotypes of rs779867 and rs6782011, and their haplotype (T-C) were statistically significantly correlated with ASD. In another population based case-control study, both rs6782011 and rs779867 were examined in 518 Iranian ASD patients and 472 control individuals and results showed that genotypes of rs779867, and haplotypes of rs779867-rs6782011 were significantly associated with ASD . A recent study extracted genomic data for 487 ASD patients and 455 healthy individuals. Among the assessed SNPs, rs6782011 of GRM7 was recognized as the one of most significant risk factors related to ASD . The discrepant finding in our study may be due to differences in phenotypic or genetic characteristics.
Serajee et al  first reported a nominally significant association of the autistic disorder with SNPs 2237731, rs712723 and rs1800656 of the GRM8 gene. In contrast, a case-control study analyzed rs1800656, rs712723, rs2237731, rs17862331 and rs17862331 of the GRM8 gene and 7 SNPs in the RFLN gene in 213 children with ASD and 160 controls in a Chinese Han population. Neither the single SNP nor the haplotype analysis showed significant association between ASD and the SNPs of the GRM8 gene . Likewise, no significant association between SNPs in the GRM8 gene and ASD was observed in our study on a Chinese Han population.
Using the CARS, we assessed overall severity of disease in children with ASD. None of the SNPs examined were associated with the severity of the disease. In contrast, Gadow et al  reported that SNP rs301430 in the SLC1A1 gene was associated with severity of repetitive behaviors and anxiety in children with ASD. Other studies found that rs2056202 and rs2292813 in the SLC25A12 gene were associated with restricted repetitive behavior , and rs2056202 was associated with severity of routines and rituals . These results suggest that some SNPs may be associated with severity of individual symptoms in patients with ASD.
There are several limitations of this case-control study. The sample size is still relatively moderate. All patients were from the local hospital and mental health facility and were receiving treatments. These untreated children with ASD were not included. Most of these untreated autistic children commonly have less severe symptoms. Furthermore, only a limited number of SNPs were selected. The severity of disease was only evaluated by the CARS. The individual symptoms of CARS were not analyzed.