5,10-methylenetetrahydrofolate reductase 677C → T and 1298A → C mutations are genetic determinants of elevated homocysteine

Maria Rita Castro, I. Rivera, P. Ravasco, C. Jakobs, H. J. Blom, M. E. Camilo, I. T. de Almeida

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalQJM - Monthly Journal of the Association of Physicians
Volume96
Issue number4
DOIs
StatePublished - Apr 1 2003

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Methylenetetrahydrofolate Reductase (NADPH2)
Homocysteine
Folic Acid
Mutation
Gene Frequency
Portugal
Homozygote
Restriction Fragment Length Polymorphisms
Population
Genes
Healthy Volunteers
Cardiovascular Diseases
Erythrocytes
Genotype
Phenotype

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Castro, Maria Rita ; Rivera, I. ; Ravasco, P. ; Jakobs, C. ; Blom, H. J. ; Camilo, M. E. ; de Almeida, I. T. / 5,10-methylenetetrahydrofolate reductase 677C → T and 1298A → C mutations are genetic determinants of elevated homocysteine. In: QJM - Monthly Journal of the Association of Physicians. 2003 ; Vol. 96, No. 4. pp. 297-303.
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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.",
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5,10-methylenetetrahydrofolate reductase 677C → T and 1298A → C mutations are genetic determinants of elevated homocysteine. / Castro, Maria Rita; Rivera, I.; Ravasco, P.; Jakobs, C.; Blom, H. J.; Camilo, M. E.; de Almeida, I. T.

In: QJM - Monthly Journal of the Association of Physicians, Vol. 96, No. 4, 01.04.2003, p. 297-303.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 5,10-methylenetetrahydrofolate reductase 677C → T and 1298A → C mutations are genetic determinants of elevated homocysteine

AU - Castro, Maria Rita

AU - Rivera, I.

AU - Ravasco, P.

AU - Jakobs, C.

AU - Blom, H. J.

AU - Camilo, M. E.

AU - de Almeida, I. T.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - 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.

AB - 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.

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