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Review
. 2014 Dec;113(4):243-52.
doi: 10.1016/j.ymgme.2014.10.006. Epub 2014 Oct 14.

Homocysteine and DNA methylation: a review of animal and human literature

Pooja R Mandaviya  1 , Lisette Stolk  2 , Sandra G Heil  3
Affiliations
Review

Homocysteine and DNA methylation: a review of animal and human literature

Pooja R Mandaviya et al. Mol Genet Metab. 2014 Dec.

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.

Keywords: B-Vitamins; DNA methylation; Homocysteine; Hyperhomocysteinemia; S-Adenosylhomocysteine; S-Adenosylmethionine.

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