Rare single nucleotide polymorphisms in the regulatory regions of the superoxide dismutase genes in autism spectrum disorder.

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.