C667T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene and susceptibility to myocardial infarction: A systematic review and meta-analysis

Int J Cardiol. 2016 Aug 15:217:99-108. doi: 10.1016/j.ijcard.2016.04.181. Epub 2016 May 4.


MTHFR C677T and A1298C polymorphisms have been reported to be associated with the risk of myocardial infarction (MI), although the results of previous studies have been inconsistent. The aim of this study was to explore whether these polymorphisms play a role in the genetic susceptibility to MI. A comprehensive search of MEDLINE and EMBASE databases was conducted for studies evaluating the association between the C667T and A1298C polymorphisms and MI risk. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated to assess the strength of association in the dominant model, recessive model, allelic model, and genotypes contrast. A total of 47 studies were finally included in this meta-analysis. Overall, the results showed no statistically significant association between C667T and A1298C polymorphisms and MI risk. However, in subgroup analysis by ethnicity, the T allele of C677T polymorphism was associated with a 63% increased risk of MI compared with the C allele (T vs. C, OR=1. 63, 95%CI=1.15-2.10, fixed effects) in African populations, while compared to wild homozygote genotype, CT genotype was associated with a decreased risk of MI in North American populations (CT vs. CC, OR=0.81, 95%CI=0.64-0.98, fixed effects). Moreover, C677T polymorphism had a protective effect against MI risk under the dominant model (OR=0.93, 945%CI=0.87-0.99, fixed effects) in elderly (≥50) population. The A1298C polymorphism was not significantly associated with MI risk. Unlike A1298C polymorphism, C677T polymorphism was associated with risk of MI in African, North American, and elderly populations.

Keywords: A1298C; C667T; MTHFR; Meta-analysis; Myocardial infarction; Polymorphism.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Age Factors
  • Alleles
  • Genetic Predisposition to Disease
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Myocardial Infarction / ethnology
  • Myocardial Infarction / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Racial Groups / genetics


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)