Homocysteine Metabolism in Children and Adolescents: Influence of Age on Plasma Biomarkers and Correspondent Genotype Interactions

Nutrients. 2019 Mar 16;11(3):646. doi: 10.3390/nu11030646.

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.

Keywords: MTHFR; folate; homocysteine; methylmalonic acid; vitamin B12.

MeSH terms

  • Adolescent
  • Age Factors*
  • Biomarkers / blood
  • Child
  • Female
  • Folic Acid / blood
  • Genotype*
  • Homocysteine / blood*
  • Homocysteine / genetics*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / blood*
  • Methylmalonic Acid / blood
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Vitamin B 12 / blood
  • Vitamin B Complex / blood

Substances

  • Biomarkers
  • Homocysteine
  • Vitamin B Complex
  • Methylmalonic Acid
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12