Genetic and environmental factors associated with homocysteine concentrations in a population of healthy young adults. Analysis of the MAGNETIC study

Nutr Metab Cardiovasc Dis. 2020 Jun 9;30(6):939-947. doi: 10.1016/j.numecd.2020.01.012. Epub 2020 Feb 12.


Background and aims: Elevated homocysteine concentration is associated with a higher risk of cardiovascular disease. The aim of our study was to determine the environmental and genetic factors associated with serum homocysteine concentration in healthy young adults. Moreover, we aimed to determine the cutoff value of homocysteine concentration for predicting unfavorable MTHFR genotype and to investigate whether this association is modified by dietary patterns and serum folate status.

Methods and results: A total of 744 healthy individuals, aged 18-35 years, were included in the study. Diet quality was assessed by establishing diet quality scores and adherence to the pro-Healthy Diet Index (pHDI) and non-Healthy Diet Index (nHDI). Genotyping was performed using the TaqMan method. Multivariate analysis showed that pHDI, creatinine, folate concentrations, and the T/T genotype of the C677T polymorphism in MTHFR, as well as the interaction between the T/T genotype of MTHFR (C677T polymorphism) and folate level, were most strongly related to homocysteine concentrations. The specificity of a homocysteine >13.1 μmol/l in predicting T/T homozygous status was 76% (area under the curve 0.68).

Conclusion: Healthy dietary patterns, folate, and creatinine levels, as well as the C677T polymorphism, proved to be the strongest predictors of homocysteine concentrations. T/T genotype of MTHFR modifies the relationship between folate and homocysteine.

Keywords: Cardiovascular disease; Coronary artery disease; Homocysteine; MTHFR; Polymorphism; Risk factors; Venous thromboembolism; rs1801133.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Biomarkers / blood
  • Creatinine / blood
  • Diet, Healthy*
  • Feeding Behavior*
  • Female
  • Folic Acid / blood
  • Gene-Environment Interaction*
  • Healthy Volunteers
  • Homocysteine / blood*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Genetic*
  • Young Adult


  • Biomarkers
  • Homocysteine
  • Folic Acid
  • Creatinine
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)