title: Homocysteine and DNA methylation: a review of animal and human literature.
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.
authors.affiliation: Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: p.mandaviya@erasmusmc.nl.
authors.forename: Pooja R
authors.initials: PR
authors.lastname: Mandaviya
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: l.stolk@erasmusmc.nl.
authors.forename: Lisette
authors.initials: L
authors.lastname: Stolk
authors.affiliation: Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: s.heil@erasmusmc.nl.
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Heil
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D019175:DNA Methylation; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D055786:Gene Knockout Techniques; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000628:therapy; D008297:Male; D008715:Methionine / Q000378:metabolism; D023421:Models, Animal; D014803:Vitamin B Complex / Q000378:metabolism / Q000627:therapeutic use; D014804:Vitamin B Deficiency / Q000178:diet therapy
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; D008715:Methionine
keywords: B-Vitamins; DNA methylation; Homocysteine; Hyperhomocysteinemia; S-Adenosylhomocysteine; S-Adenosylmethionine