Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children

Gątarek, Paulina; Rosiak, Angelina; Borowczyk, Kamila; Głowacki, Rafał; Kałużna–Czaplińska, Joanna

doi:10.3390/molecules25040973

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…Potential explanations may be due to sex-related differences in the prevalence and effects of polymorphic gene variants [55]. Accordingly, anomalous transsulfuration pathway and dysregulated folate or Hcy metabolism may lead to aberrant redox homeostasis and neurodegeneration, and in turn, increased ASD susceptibility [56][57][58]. Several studies have indeed reported a correlation between high Hcy and low folate, vitamin B6, and B12 levels with ASD and severity [58,59].…”

Section: One-carbon Metabolism Pathwaymentioning

confidence: 99%

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

Tisato

Silva

Longo

et al. 2021

Genes

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting behavior and communication, presenting with extremely different clinical phenotypes and features. ASD etiology is composite and multifaceted with several causes and risk factors responsible for different individual disease pathophysiological processes and clinical phenotypes. From a genetic and epigenetic side, several candidate genes have been reported as potentially linked to ASD, which can be detected in about 10–25% of patients. Folate gene polymorphisms have been previously associated with other psychiatric and neurodegenerative diseases, mainly focused on gene variants in the DHFR gene (5q14.1; rs70991108, 19bp ins/del), MTHFR gene (1p36.22; rs1801133, C677T and rs1801131, A1298C), and CBS gene (21q22.3; rs876657421, 844ins68). Of note, their roles have been scarcely investigated from a sex/gender viewpoint, though ASD is characterized by a strong sex gap in onset-risk and progression. The aim of the present review is to point out the molecular mechanisms related to intracellular folate recycling affecting in turn remethylation and transsulfuration pathways having potential effects on ASD. Brain epigenome during fetal life necessarily reflects the sex-dependent different imprint of the genome-environment interactions which effects are difficult to decrypt. We here will focus on the DHFR, MTHFR and CBS gene-triad by dissecting their roles in a sex-oriented view, primarily to bring new perspectives in ASD epigenetics.

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Section: One-carbon Metabolism Pathwaymentioning

confidence: 99%

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

Tisato

Silva

Longo

et al. 2021

Genes

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“…A point mutation in the gene encoding MTHFR , which is located on chromosome 1p36.3, is associated with several malignancies, including colon cancer, gastric cancer, lung cancer, esophageal squamous cell carcinoma, breast cancer, and gynecological cancer ( 11 – 18 ). MTHFR is a critical enzyme involved in the folate metabolism pathway and DNA methylation and synthesis ( 19 ). The MTHFR C677T, a cytosine (C) to a thymine (T) substitution at position 677, which changes an alanine to a valine, leads to impaired folate binding and reduced MTHFR activity ( 20 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors

Yan

Xue

et al. 2022

Front. Oncol.

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ObjectiveTo describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of TETs.MethodsPathological records were reviewed from the database of the Second Affiliated Hospital of Jiaxing University, from January 2010 to December 2020, and 84 patients with TETs were recruited for this study. Univariate and multivariate analyses were performed to determine the prognostic factors. The genetic polymorphism of MTHFR C667T was examined in the patients with TETs and in a group of healthy individuals. The correlation between MTHFR transcriptional levels and methylation was analyzed using The Cancer Genome Atlas (TCGA) thymoma dataset from the cBioPortal platform.ResultsKaplan–Meier univariate survival analysis showed that sex, age, the maximum tumor diameter, surgery, chemotherapy, radiotherapy, WHO histological classification, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging, were statistically significantly correlated with the prognosis of patients with TETs. The Masaoka–Koga stage and 8th UICC/AJCC TNM staging were strongly correlated with each other in this study (r=0.925, P<0.001). Cox multivariate survival analysis showed that the maximum tumor diameter, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging were independent prognostic factors affecting the overall survival (OS) of patients with TETs (P<0.05). The MTHFR C667T genotype (χ2 = 7.987, P=0.018) and allele distribution (χ2 = 5.750, P=0.016) were significantly different between the patients and healthy controls. CT heterozygous and TT homozygous genotypes at this MTHFR polymorphism significantly increased the risk of TETs (odds ratio [OR] =4.721, P=0.008). Kaplan–Meier univariate survival analysis showed that there was no correlation between different genotypes and the prognosis of TETs (CC versus CT + TT, χ2 =0.003, P=0.959). Finally, a negative correlation between the transcriptional and methylation levels of MTHFR was observed in the TCGA thymoma dataset (r=-0.24, P=0.010).ConclusionsThe Masaoka–Koga stage, 8th UICC/AJCC TNM staging, and maximum tumor diameter were independent prognostic factors for TETs. Reduced methylation levels of MTHFR and particular polymorphic variants may contribute to the susceptibility to developing TETs.

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“…Homocysteine thiolactone (HTL) is a well-known modifying factor of proteins, and its role in the pathogenesis of different diseases has started to be recognized [ 1 , 2 , 3 , 4 ]. HTL is a chemically reactive metabolite generated by methionyl-tRNA synthetase and cleared by the kidney [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Single-Step Hydrolysis and Derivatization of Homocysteine Thiolactone Using Zone Fluidics: Simultaneous Analysis of Mixtures with Homocysteine Following Separation by Fluorosurfactant-Modified Gold Nanoparticles

2022

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Herein, we report a new automated flow method based on zone fluidics for the simultaneous determination of homocysteine and homocysteine thiolactone using fluorimetric detection (λext = 370 nm/λem = 480 nm). Homocysteine thiolactone is hydrolyzed on-line in alkaline medium (1 mol L−1 NaOH) to yield homocysteine, followed by reaction with o-phthalaldehyde in a single step. Derivatization is rapid without the need of elevated temperatures and stopped-flow steps, while specificity is achieved through a unique reaction mechanism in the absence of nucleophilic compounds. Mixtures of the analytes can be analyzed quantitatively after specific separation with fluorosurfactant-capped gold nanoparticles that are selectively aggregated by homocysteine, leaving the thiolactone analogue in solution. As low as 100 nmol L−1 of the analyte(s) can be quantified in aqueous solutions, while concentrations > 2 μmol L−1 can be analyzed in artificial and real urine matrix following 20-fold dilution. The percent recoveries ranged between 87 and 119%.

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Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children

Cited by 8 publications

References 58 publications

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors

Single-Step Hydrolysis and Derivatization of Homocysteine Thiolactone Using Zone Fluidics: Simultaneous Analysis of Mixtures with Homocysteine Following Separation by Fluorosurfactant-Modified Gold Nanoparticles

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