title: Genetic variants of methionine metabolism and DNA methylation.
abstract: OBJECTIVE
  Altered DNA methylation is associated with important and common pathologies such as cancer. The origin of altered DNA methylation is unknown. The methyl groups for DNA methylation are provided by methionine metabolism. This metabolism is characterized by a high interindividual variability, which is in part explained by genetic variants.
  
  
  METHODS
  In a cohort of 313 individuals derived from a family-based study with index cases of cerebrovascular disease, we analyzed whether global methylation of leukocyte DNA was associated with age, gender, homocysteine plasma levels or functionally relevant genetic variants.
  
  
  RESULTS
  We observed an association of the G-allele of the methionine synthase variant c.2756A>G (D919G) with global methylation (% methylation ± 1 SD, AA: 41.3 ± 14.9; AG: 36.4 ± 18.2; GG: 30.8 ± 16.9; F = 4.799; p = 0.009). The methionine synthase variant c.2756A>G is associated with various types of cancer.
  
  
  CONCLUSIONS
  Our data suggest that an impact on DNA methylation may contribute to the clinical relevance of the methionine synthase variant.
authors.affiliation: Molecular Neuroscience Laboratory, Department of Psychiatry, Social Psychiatry & Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.forename: Alexander
authors.initials: A
authors.lastname: Semmler
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.forename: L
authors.initials: L
authors.lastname: Thumfart
authors.forename: Marc
authors.initials: M
authors.lastname: Muschler
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Ulf
authors.initials: U
authors.lastname: Kallweit
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002561:Cerebrovascular Disorders / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D014644:Genetic Variation; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D006710:Homocysteine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human
keywords: DNA methylation; homocysteine; methionine metabolism; single nucleotide polymorphism