Abstract

Background: Imbalance of homocysteine (Hcy) metabolism links with several pathologies; nevertheless, it is poorly characterized in pediatric populations. This study investigated the impact of age on plasma concentrations of Hcy and relevant biomarkers along with correspondent genotype interactions. Methods: A healthy pediatric cohort aged 9 (n = 195) and 17 (n = 128) years old (yo) was studied. Immunoassays and GC-MS-SIM-mode quantified plasma levels of Hcy and biomarkers. PCR-RFLP or quantitative-PCR assays assessed common variations in related genes. Results: Age impacted on levels of Hcy and metabolic markers: older children presented with the lowest folates and total-cobalamin (tCbl), while with the highest Hcy concentrations, whereas methylmalonic acid (MMA) and holotranscobalamin (Holo-TC) levels remained similar in 9-yo and 17-yo children. The relationships between B-vitamins and metabolic markers were also dependent on age. Only in the older children, MMA correlated with tCbl and Holo-TC, and MMA levels were markedly higher in the 17-yo subjects presenting with the lowest quartiles of Holo-TC concentrations. Lastly, age also impacted on the correlations between genotype and biomarkers. In the 17-yo group, however not in the 9-yo children, tHcy differed between MTHFR 677 genotypes, with subjects who had the MTHFR 677TT genotype displaying the highest tHcy concentrations. Conclusions: Age impacts on the Hcy metabolism dynamics in a pediatric population.

Highlights

  • The homocysteine (Hcy) metabolism is a metabolic network centered on the folate and methionine cycles in which one-carbon (1-C) groups are transferred, supporting multiple physiological processes, including nucleotide biosynthesis, amino acid homeostasis, epigenetic maintenance and redox defense [1,2]

  • All the included individuals were eutrophic according to Body Mass Index (BMI) cut-off values of the World Health Organization (WHO) Growth Reference

  • The study of genetic variants related to Hcy metabolism in young pediatric populations may allow for better knowledge of native phenotypes, as time was not enough for environmental factors to modify them substantially

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Summary

Introduction

The homocysteine (Hcy) metabolism is a metabolic network centered on the folate and methionine cycles in which one-carbon (1-C) groups are transferred, supporting multiple physiological processes, including nucleotide biosynthesis, amino acid homeostasis, epigenetic maintenance and redox defense [1,2]. The metabolisms of Hcy, folate and vitamin B12 (or cobalamin, Cbl) are biochemically linked sharing several metabolic intermediates [9]. Once formed, Hcy may be conserved and remethylated back to methionine by methionine synthase (MS). This enzyme requires the presence of methylcobalamin (methylCbl), as a cofactor, to carry on its function. This study investigated the impact of age on plasma concentrations of Hcy and relevant biomarkers along with correspondent genotype interactions. Results: Age impacted on levels of Hcy and metabolic markers: older children presented with the lowest folates and total-cobalamin (tCbl), while with the highest Hcy concentrations, whereas methylmalonic acid (MMA) and holotranscobalamin (Holo-TC) levels remained similar in 9-yo and 17-yo children

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