title: Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age.
abstract: BACKGROUND
  Elevated fasting levels of total homocysteine are now accepted as an independent risk factor for the development of arteriosclerotic vascular diseases. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), caused by the C677T point mutation, leads to increased thermolability of the enzyme, with reduced enzyme activity. We studied the frequency of this mutation in different groups of the Swiss adult population.
  
  
  METHODS
  DNA from 361 subjects was screened for the thermolabile MTHFR variant with PCR. Included were healthy subjects without vascular disease (n = 118), older healthy subjects (n = 106), patients with coronary artery disease (CAD, n = 75), and patients with peripheral arterial occlusive disease (PAOD, n = 63).
  
  
  RESULTS
  In the different groups studied, homozygosity for the mutation ranged from 4.8 to 16.2%, with a frequency of 16.2% in the healthy cohort. The allele frequencies of the thermolabile allele were 38.5 and 27.3 in young and old controls, and 37.3 and 33.3 in CAD and PAOD patients. In the healthy younger subjects the mutant allele was 1.4 times more frequent compared to the older subjects (P = 0.01). No difference in either MTHFR genotype distribution (P = 0.33) or allele frequencies (P = 0.48) between patients and controls was found. Except for the PAOD group with elevated tHcy levels for the +/+ carriers compared to the other genotypes, no statistically significant difference was found comparing homocysteine levels with genotype.
  
  
  CONCLUSIONS
  This study shows no link between the mutation and the occurrence of vascular disease but we found evidence pointing to a correlation between the mutation and longevity in our population.
authors.affiliation: Department of Internal Medicine, Kantonsspital Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Todesco
authors.forename: C
authors.initials: C
authors.lastname: Angst
authors.forename: P
authors.initials: P
authors.lastname: Litynski
authors.forename: F
authors.initials: F
authors.lastname: Loehrer
authors.forename: B
authors.initials: B
authors.lastname: Fowler
authors.forename: W E
authors.initials: WE
authors.lastname: Haefeli
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)