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Genetic determinants of plasma total homocysteine

Henkjan Gellekink1, Martin den Heijer, Sandra G Heil

  • 1Laboratory of Pediatrics and Neurology (424), Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Seminars in Vascular Medicine
|July 28, 2005
PubMed

Insights

High homocysteine (Hhcy) is linked to vascular disease and dementia. This review examines genetic variations in homocysteine and B-vitamin metabolism, identifying key polymorphisms associated with elevated Hhcy levels in populations.

Area of Science:

  • Biochemistry and Genetics
  • Metabolic Disorders
  • Cardiovascular and Neurological Diseases

Background:

  • Hyperhomocysteinemia (Hhcy) is a recognized risk factor for arterial vascular disease, venous thrombosis, congenital malformations, pregnancy complications, and dementia.
  • Homocysteine levels are regulated by remethylation, transsulfuration, and extracellular export pathways; disruptions can lead to Hhcy and associated pathologies.

Purpose of the Study:

  • To review known genetic polymorphisms influencing homocysteine and B-vitamin metabolism.
  • To assess the impact of these polymorphisms on total homocysteine (tHcy) levels.
  • To identify genetic determinants of Hhcy at the population level.

Main Methods:

  • Comprehensive literature review of studies investigating polymorphisms in homocysteine and B-vitamin metabolic pathways.
  • Analysis of data linking specific polymorphisms to altered total homocysteine (tHcy) concentrations.
  • Synthesis of evidence for population-level associations between genetic variations and Hhcy.

Main Results:

  • Identified numerous polymorphisms within homocysteine and B-vitamin metabolism pathways.
  • Summarized evidence supporting the role of specific polymorphisms in contributing to Hhcy at the population level.
  • Highlighted polymorphisms with established links to increased risk of Hhcy-related diseases.

Conclusions:

  • Genetic variations significantly impact homocysteine levels and contribute to Hhcy.
  • Certain polymorphisms are confirmed population-level determinants of Hhcy.
  • Further research is warranted to fully elucidate the genetic architecture of tHcy and its clinical implications.

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