Abstract
Homocysteine (Hcy) is a sulfur-containing non-protein forming amino acid, which is synthesized from methionine as an important intermediate in the one-carbon pathway. High concentrations of Hcy in a condition called hyperhomocysteinemia (HHcy) are an independent risk factor for several disorders including cardiovascular diseases and osteoporotic fractures. Since Hcy is produced as a byproduct of the methyltransferase reaction, alteration in DNA methylation is studied as one of the underlying mechanisms of HHcy-associated disorders. In animal models, elevated Hcy concentrations are induced either by diet (high methionine, low B-vitamins, or both), gene knockouts (Mthfr, Cbs, Mtrr or Mtr) or combination of both to investigate their effects on DNA methylation or its markers. In humans, most of the literature involves case-control studies concerning patients. The focus of this review is to study existing literature on HHcy and its role in relation to DNA methylation. Apart from this, a few studies investigated the effect of Hcy-lowering trials on restoring DNA methylation patterns, by giving a folic acid or B-vitamin supplemented diet. These studies which were conducted in animal models as well as humans were included in this review.
Original language | English |
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Pages (from-to) | 243-52 |
Number of pages | 10 |
Journal | Molecular Genetics and Metabolism |
Volume | 113 |
Issue number | 4 |
DOIs | |
Publication status | Published - Dec 2014 |
Externally published | Yes |
Keywords
- Animals
- Case-Control Studies
- DNA Methylation
- Diet
- Dietary Supplements
- Female
- Folic Acid/administration & dosage
- Gene Knockout Techniques
- Homocysteine/metabolism
- Humans
- Hyperhomocysteinemia/therapy
- Male
- Methionine/metabolism
- Models, Animal
- Vitamin B Complex/metabolism
- Vitamin B Deficiency/diet therapy