Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: The A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal)

Ana I. Freitas, Isabel Mendonça, Graça Guerra, Maria Brión, Roberto P. Reis, Angel Carracedo, António Brehm

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
1 Downloads (Pure)


Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on fasting homocysteine and CAD in 298 CAD patients proved by angiography and 510 control subjects from the Island of Madeira (Portugal). After adjustment for other risk factors, plasma homocysteine remained independently correlated with CAD. Serum homocysteine was significantly higher in individuals with 677TT and 1298AA genotypes. There was no difference in the distribution of MTHFR677 genotypes between cases and controls but a significant increase in 1298AA prevalence was found in CAD patients. In spite of the clear effect of C677T mutation on elevated homocysteine levels we only found an association between 1298AA genotype and CAD in this population. The simultaneous presence of 677CT and 1298AA genotypes provides a significant risk of developing the disease, while the 1298AC genotype, combined with 677CC, shows a significant trend towards a decrease in CAD occurrence. The data shows an independent association between elevated levels of homocysteine and CAD. Both MTHFR polymorphisms are associated with increased fasting homocysteine (677TT and 1298AA genotypes), but only the 1298AA variant shows an increased prevalence in CAD group. Odds ratio seem to indicate that individuals with the MTHFR 1298AA genotype and the 677CT/1298AA compound genotype had a 1.6-fold increased risk for developing CAD suggesting a possible association of MTHFR polymorphisms with the risk of CAD in Madeira population.

Original languageEnglish
Pages (from-to)648-656
Number of pages9
JournalThrombosis Research
Issue number5
Publication statusPublished - 2008


  • Coronary artery disease
  • Gene polymorphisms
  • Homocysteine


Dive into the research topics of 'Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: The A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal)'. Together they form a unique fingerprint.

Cite this