title: 5,10-Methylenetetrahydrofolate reductase 677C-->T and 1298A-->C mutations are genetic determinants of elevated homocysteine.
abstract: BACKGROUND
  Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Elevated plasma total homocysteine (tHcy) is a major risk for cardiovascular disease. A common 677C-->T mutation in the MTHFR gene results in decreased enzymic activity, and contributes to increased plasma tHcy, in association with low plasma folate. A recently described 1298A-->C mutation in the MTHFR gene clearly reduces MTHFR activity (although to a lesser extent than the 677C-->T) but its effect on plasma tHcy levels is not yet clear.
  
  
  OBJECTIVE
  To investigate the frequency of these two MTHFR polymorphisms in a Portuguese population, and to correlate the MTHFR genotype with the biochemical phenotype at the level of homocysteine and folate concentrations.
  
  
  METHODS
  Prospective population survey.
  
  
  METHODS
  We studied 117 healthy volunteers (71 females, 46 males). The 677C-->T and 1298A-->C mutations were screened by PCR-RFLP. Levels of plasma tHcy and folate, and red blood cell folate, were determined.
  
  
  RESULTS
  The allele frequencies of the 677C-->T and 1298A-->C mutations were 0.33 and 0.28, respectively. Homozygotes for the 677C-->T mutation had significantly elevated plasma tHcy and RBC folate levels and significantly lowered plasma folate concentrations than subjects without the mutation. The 1298A-->C mutation showed a significant effect on plasma tHcy, but not on plasma folate or RBC folate levels.
  
  
  CONCLUSIONS
  The observed 677T allele frequency is not consistent with the idea of a north-south gradient as previously suggested. The 1298A-->C mutation is common in Portugal. Both MTHFR mutations showed effects on plasma tHcy levels.
authors.affiliation: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Castro
authors.forename: I
authors.initials: I
authors.lastname: Rivera
authors.forename: P
authors.initials: P
authors.lastname: Ravasco
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: M E
authors.initials: ME
authors.lastname: Camilo
authors.forename: I T
authors.initials: IT
authors.lastname: de Almeida
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000328:Adult; D000368:Aged; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D011174:Portugal; D011446:Prospective Studies
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2)