5,10-Methylenetetrahydrofolate reductase 677C-->T and 1298A-->C mutations are genetic determinants of elevated homocysteine. QJM : monthly journal of the Association of Physicians. [QJM] Journal article | | Title | 5,10-Methylenetetrahydrofolate reductase 677C-->T and 1298A-->C mutations are genetic determinants of elevated homocysteine. | | Author(s) | Castro R, Rivera I, Ravasco P, Jakobs C, Blom HJ, Camilo ME, de Almeida IT | | Institution | Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Portugal. | | Source | QJM 2003 Apr; 96(4):297-303. | | MeSH | 5,10-Methylenetetrahydrofolate Reductase (FADH2)
Adult
Aged
Female
Folic Acid
Gene Frequency
Homocysteine
Humans
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Mutation
Oxidoreductases
Portugal
Prospective Studies
Research Support, Non-U.S. Gov't
| | 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.
AIM: 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.
DESIGN: 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.
DISCUSSION: 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12651974 |
|
|
| |
Advertise on this site.
| | |
|
