title: Rare single nucleotide polymorphisms in the regulatory regions of the superoxide dismutase genes in autism spectrum disorder.
abstract: 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.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, UMC Ljubljana, University Children's Hospital, Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Kovač
authors.forename: Marta
authors.initials: M
authors.lastname: Macedoni Lukšič
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebušak Podkrajšek
authors.forename: Gašper
authors.initials: G
authors.lastname: Klančar
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017524:Slovenia; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C441642:SOD3 protein, human
keywords: ROS; autism spectrum disorder; genetic variants; oxidative stress; superoxide dismutase