The prevalence of the autism spectrum disorder (ASD) was recently estimated to 1 in 88 children by the CDC MMWR. In up to 25 % of the cases, the genetic cause can be identified. Past studies identified increased level of advanced glycation end products (AGE) in the brain samples of ASD patients. The methylglyoxal (MG) is one of the main precursors for AGE formation. Humans developed effective mechanism of the MG metabolism involving two enzymes glyoxalase 1 (GLO1) and hydroxyacylglutathione hydrolase (HAGH). Our aim was to analyse genetic variants of GLO1 and HAGH in population of 143 paediatric participants with ASD. We detected 7 genetic variants in GLO1 and 16 variants in HAGH using high-resolution melting (HRM) analysis. A novel association between variant rs1049346 and ASD [OR (allele C)] = 1.5; 95 % CI = 1.1-2.2 and p < 0.05) was identified, and weak association between ASD and variant rs2736654 [OR (allele A)] = 2.2; 95 % CI = 0.99-4.9; p = 0.045) was confirmed. Additionally, a novel genetic variant (GLO1 c.484G > A, p.Ala161Thr) with predicted potentially damaging effect on the activity of the glyoxalase 1 that may contribute to the aetiology of ASD was identified in one participant with ASD. No association between genetic variants of the HAGH gene and ASD was found. Increased level of MG and, consequently, AGEs can induce oxidative stress, mitochondrial dysfunction and inflammation all of which have been implicated to act in the aetiology of the ASD. Our results indicate potential importance of MG metabolism in ASD. However, these results must be interpreted with caution until a causative relation is demonstrated.

Oxidative stress is suspected to be one of the several contributing factors in the etiology of autism spectrum disorder (ASD). We analyzed genes of the superoxide dismutase family (SOD1, SOD2, and SOD3) that are part of a major antioxidative stress system in human in order to detect the genetic variants contributing to the development of ASD. Using the optimized high-resolution melting (HRM) analysis, we identified two rare single nucleotide polymorphisms (SNPs) associated with the etiology of ASD. Both are located in the superoxide dismutase 1 (SOD1) gene and have a minor allele frequency in healthy population ~5%. The SNP c.239 + 34A>C (rs2234694) and SNP g.3341C>G (rs36233090) were detected with an odds ratio of 2.65 and P < 0.01. Both are located in the noncoding potentially regulatory regions of the SOD1 gene. This adds to the importance of rare SNPs in the etiology of complex diseases as well as to the importance of noncoding genetic variants analysis with a potential influence on the regulation of gene expression.