Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis

J Hum Genet. 2003;48(1):1-7. doi: 10.1007/s100380300000.


Common single nucleotide polymorphisms (SNPs; 677C>T and 1298A>C) in the methylenetetrahydrofolate reductase gene ( MTHFR) decrease the activity of the enzyme, leading to hyperhomocysteinemia, particularly in folate-deficient states. We calculate herein the haplotype frequencies of the MTHFR 677 and 1298 polymorphisms in pooled general populations derived from published data. We selected 16 articles that provided reliable data on combined MTHFR genotypes in general populations ( n = 5389). The combined data comprised the following totals for each genotype at nucleotide positions 677 and 1298: 838 CC/AA (i.e., 677CC/1298AA), 1225 CC/AC, 489 CC/CC, 1120 CT/AA, 1093 CT/AC, 8 CT/CC, 606 TT/AA, 10 TT/AC, and 0 TT/CC. The estimated haplotype frequencies, and the fractional contribution of each, were 677C/1298A, 0.37; 677C/1298C, 0.31; 677T/1298A, 0.32; and 677T/1298C, 0.0023 to 0.0034. Thus, a vast majority of 677T alleles and 1298C alleles are associated with 1298A alleles and 677C alleles, respectively. There may be an increased frequency of the very rare cis 677T/1298C haplotype in some parts of the United Kingdom and Canada, possibly due to a founder effect. Further studies on both SNPs are needed to determine their exact role in various clinical settings.

Publication types

  • Meta-Analysis

MeSH terms

  • Genotype
  • Haplotypes*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Polymorphism, Single Nucleotide*


  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)