Dataset Information

Exploration of homocysteine metabolism and genetics in Autism Spectrum Disorder

ABSTRACT: This project investigated the genetic and metabolic profiles of Lebanese children and adolescents with Autism Spectrum Disorder (ASD) to better understand the disorder’s etiology and identify potential biomarkers. Specifically, the study focused on methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (rs1801133 and rs1801131) and their relationship with homocysteine metabolism, as well as plasma levels of vitamin B9, vitamin B12, glucose, and lipid profiles. A total of 172 participants (86 individuals with ASD and 86 age-, sex-, and region-matched neurotypical controls) aged between 3 and 18 years were recruited across Lebanon between June 2022 and June 2023. ASD diagnosis was confirmed using DSM-5 criteria and the Childhood Autism Rating Scale (CARS). Blood samples were collected under fasting conditions to measure biochemical parameters (homocysteine, vitamin B9, vitamin B12, glucose, lipid panel), while DNA was extracted for genotyping of the MTHFR variants using PCR and Sanger sequencing. The results revealed that while the MTHFR rs1801133 and rs1801131 polymorphisms were not significantly associated with ASD risk, individuals with ASD had significantly higher homocysteine levels and lower vitamin B9 concentrations compared to controls. Vitamin B12, glucose, and lipid concentrations showed no significant group differences. However, the TT genotype of the rs1801133 variant was strongly associated with elevated homocysteine levels among individuals with ASD. These findings suggest that hyperhomocysteinemia and folate deficiency may contribute to the pathophysiology of ASD, highlighting their potential role as metabolic biomarkers. Although no direct genetic association was observed between MTHFR variants and ASD susceptibility in the Lebanese population, the correlation between the rs1801133 TT genotype and elevated homocysteine underscores the importance of integrating genetic and metabolic data. This work represents the first Lebanese case-control study combining genetic and biochemical approaches to ASD. It emphasizes the need for further research on metabolic pathways, nutritional interventions (particularly folate supplementation), and additional enzymes involved in homocysteine metabolism. Ultimately, this project aims to contribute to the development of personalized intervention strategies and improve understanding of ASD within the Middle Eastern context.

INSTRUMENT(S): -

ORGANISM(S): Homo Sapiens

SUBMITTER: Holy Spirit University of Kaslik and University of Tours

PROVIDER: PRJEB96538 | EVA | 2025-08-30

REPOSITORIES: EVA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MTHFR_ASD_study_GRCh38.vcf.csi	Other
	MTHFR_ASD_study_GRCh38.vcf.gz	Vcf
	MTHFR_ASD_study_GRCh38.vcf.gz.csi	Vcf

Items per page:

1 - 3 of 3

Similar Datasets

Project description:Background---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes. Methods and Results---No significant correlation was found between leukocyte counts and plasma lipid levels in 74 individuals. Profiling and analyzing the leukocyte gene expression of 32 individuals revealed distinctive patterns in response to plasma lipid levels: 1) genes involved in lipid metabolism and in the electron transport chain were positively correlated with triglycerides and low-density lipoprotein cholesterol levels, and negatively correlated with high-density lipoprotein cholesterol levels; 2) genes involved in platelet activation were negatively correlated with high-density lipoprotein cholesterol levels; 3) transcription factors regulating lipidgenesis-related genes were correlated with plasma lipid levels; 4) a number of genes correlated to plasma lipid levels were found located in the regions of known QTLs associated with hyperlipemia. Conclusions--- We discovered interesting patterns of leukocyte gene expression in response to plasma lipid levels. Most importantly, genes involved in lipid metabolism, the electron transportation chain, and platelet activation were found correlated with plasma lipid levels. We suggest that leukocytes respond to changing plasma lipid levels by regulating a network of genes, including genes involved in lipid and fatty acid metabolism, through the activation of key transcription factors, such as sterol regulatory element binding transcription factors and peroxisome proliferative activated receptors. Experiment Overall Design: 1. Profile gene expression in human peripheral blood cells. Experiment Overall Design: 2. Test blood biochemistry and blood cell differential counts Experiment Overall Design: 3. Examine the correlation between blood gene expression and blood lipid levels. Experiment Overall Design: 4. Explore possible pathways with significant genes. Experiment Overall Design: 5. Validate a number of significant genes with RT-PCR

Project description:Background---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes. Methods and Results---No significant correlation was found between leukocyte counts and plasma lipid levels in 74 individuals. Profiling and analyzing the leukocyte gene expression of 32 individuals revealed distinctive patterns in response to plasma lipid levels: 1) genes involved in lipid metabolism and in the electron transport chain were positively correlated with triglycerides and low-density lipoprotein cholesterol levels, and negatively correlated with high-density lipoprotein cholesterol levels; 2) genes involved in platelet activation were negatively correlated with high-density lipoprotein cholesterol levels; 3) transcription factors regulating lipidgenesis-related genes were correlated with plasma lipid levels; 4) a number of genes correlated to plasma lipid levels were found located in the regions of known QTLs associated with hyperlipemia. Conclusions--- We discovered interesting patterns of leukocyte gene expression in response to plasma lipid levels. Most importantly, genes involved in lipid metabolism, the electron transportation chain, and platelet activation were found correlated with plasma lipid levels. We suggest that leukocytes respond to changing plasma lipid levels by regulating a network of genes, including genes involved in lipid and fatty acid metabolism, through the activation of key transcription factors, such as sterol regulatory element binding transcription factors and peroxisome proliferative activated receptors. Keywords: Atherosclerosis, leukocyte, lipid, gene expression

Dataset Information

Exploration of homocysteine metabolism and genetics in Autism Spectrum Disorder

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets