caa a22 4500 60547642X CHVBK 20210128100356.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00787-014-0537-8 doi (NATIONALLICENCE)springer-10.1007/s00787-014-0537-8 Weak association of glyoxalase 1 ( GLO1 ) variants with autism spectrum disorder [Elektronische Daten] [Jernej Kovač, Katarina Podkrajšek, Marta Lukšič, Tadej Battelino] 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. Springer-Verlag Berlin Heidelberg, 2014 ASD nationallicence Association study nationallicence Genetics nationallicence Glyoxalase 1 nationallicence Methylglyoxal nationallicence Kovač Jernej Department of Endocrinology, Diabetes and Metabolic Diseases, UMC Ljubljana, University Children's Hospital, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia aut Podkrajšek Katarina Centre of Medical Genetics, UMC Ljubljana, University Children's Hospital, Vrazov trg 1, 1000, Ljubljana, Slovenia aut Lukšič Marta Department of Child, Adolescent and Developmental Neurology, Centre for Autism, UMC Ljubljana, University Children's Hospital, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia aut Battelino Tadej Department of Endocrinology, Diabetes and Metabolic Diseases, UMC Ljubljana, University Children's Hospital, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia aut European Child & Adolescent Psychiatry Springer Berlin Heidelberg 24/1(2015-01-01), 75-82 1018-8827 24:1<75 2015 24 787 https://doi.org/10.1007/s00787-014-0537-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00787-014-0537-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kovač Jernej Department of Endocrinology, Diabetes and Metabolic Diseases, UMC Ljubljana, University Children's Hospital, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Podkrajšek Katarina Centre of Medical Genetics, UMC Ljubljana, University Children's Hospital, Vrazov trg 1, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Lukšič Marta Department of Child, Adolescent and Developmental Neurology, Centre for Autism, UMC Ljubljana, University Children's Hospital, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 700 1- Battelino Tadej Department of Endocrinology, Diabetes and Metabolic Diseases, UMC Ljubljana, University Children's Hospital, Bohoričeva ulica 20, 1000, Ljubljana, Slovenia aut NATIONALLICENCE 773 0- European Child & Adolescent Psychiatry Springer Berlin Heidelberg 24/1(2015-01-01), 75-82 1018-8827 24:1<75 2015 24 787