Weak association of glyoxalase 1 (GLO1) variants with autism spectrum disorder

Abstract

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.

The influence of glyoxalase 1 gene polymorphism on its expression at different stages of breast cancer in Egyptian women

“…GLO1 gene polymorphism has been reported in some diseases other than breast cancer including, diabetes mellitus and its complications [ 22 , 23 ], epilepsy [ 24 ] and autism spectrum disorder [ 25 ]. GLO1 CC genotype of (rs4746) polymorphism was associated with significantly higher prevalence of peripheral vascular and cardiovascular diseases in hemodialysis patients [ 26 ].…”

Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study

“…Shared common genes between ASD and type 2 DM may increase the risk of type 2 DM in patients with ASD (9,10,(28)(29)(30)(31). GLO1, an enzyme involved in the detoxification of methylglyoxal and in limiting the advanced glycation end products formation, is crucial in autism susceptibility and type 2 DM disease progression (9,10,29,31).…”

“…GLO1, an enzyme involved in the detoxification of methylglyoxal and in limiting the advanced glycation end products formation, is crucial in autism susceptibility and type 2 DM disease progression (9,10,29,31). In addition, Belligni et al (28) reported that a patient with a de novo duplication on chromosome 17p13.1 involving neuroligin 2, ephrin B3, and GLUT type 4 genes manifested obesity, type 2 DM, intelligence disability, and autistic traits.…”

“…Jones et al (8) monitored 92 patients with ASD from their childhood to adulthood and found that ;10% of the patients were diagnosed with type 2 DM in their adulthood. Several genetic studies also suggested that ASD and type 2 DM may share similar common gene polymorphisms, such as glyoxalase I (GLO1) C419A polymorphism (9,10). The above studies have several limitations, however, including a small sample size, a cross-sectional study design incapable of clarifying the temporal association between ASD and type 2 DM, and an adult ASD population instead of an adolescent population.…”

Fifty-Five years of Pediatric Endocrinology and 50 years of the Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases in Slovenia / 55 Let Pediatrične Endokrinologije in 50 Let Kliničnega Oddelka Za Endokrinologijo, Diabetes in Presnovne Bolezni Pediatrične Klinike

“…The department has a strong vision to further increase integration into European research structures (it currently participates in two ESPE research grants, in two EU grants, and has three grants from the Slovene National Research Agency), quality assurance programs (it obtained the SWEET-IDF-ISPAD certificate in 2014) and clinical excellence. Finally, tight cooperation with the Laboratory for Medical Genetics at the UCH Ljubljana also fosters applied basic research ( 11 – 19 ).…”