GFOL: Methylation cycle polymorphisms

677C-T and 1298A-C are two SNP’s in the gene coding for MTHFR (methylene tetrahydrofolate reductase).The T allele of 677C-T, and the C allele of 1298A-C are the “bad” alleles, corresponding to a low activity form of MTHFR. The low activity leads to accumulation of homocysteine, and low levels of folate.

Results are reported as “high activity”, “moderate activity”, or “low activity”, corresponding to the following genotypes:


  • C/C genotype: high activity
  • C/T genotype: moderate activity
  • T/T genotype: low activity


  • A/A genotype: high activity
  • A/C genotype: moderate activity
  • C/C genotype: low activity

The total activity of MTHFR depends on the combination of both SNP’s. The worst is “low activity” on both.

MTHFR is involved in biological pathways related to DNA synthesis, DNA methylation (important for gene regulation), neurotransmitter synthesis, myelin synthesis and glutathione synthesis (important for detoxification and antioxidant activities). Folic acid itself, is a strong antioxidant.

There is a link between folate deficiency and cancer (notably prostate cancer) but benefits from folate supplementation in cancer is a controversial subject.

Folate may prevent the appearance of cancer but since it is important for rapidly dividing cells (because it is needed for DNA synthesis) it could actually promote the growth of tumors, once they’re established.

GVDR: Polymorphisms of Vitamin D receptor

Bsm1 and Fok1 are two SNP’s in the gene coding for VDR (vitamin D receptor).VDR is not only involved in skeletal metabolism but also in modulation of immune response, regulation of cell proliferation and differentiation. VDR dysfunction has been linked with osteoarthritis, cancer, diabetes and cardiovascular disease.

Fok1 is a T-C polymorphism. The T allele leads to a protein, which is less effective in transducing the vitamin D signal. This allele may be associated with certain cancers (ovarian cancer), as well as Crohn’s disease. According to Ruggiero’s abstract people with T allele have a lower response to GcMAF. People with C allele have a higher response. Heterozygotes will have a moderate response. Other Bsm1 is a C-T polymorphism. The C allele is associated with Th1 suppression and breast cancer, the T allele with SLE and RA. Therefore there may be a link between VDR polymorphism and Th1/Th2 balance.


  • C/C genotype: high responder (FF genotype)
  • T/C genotype: moderate responder (Ff genotype)
  • T/T genotype: low responder (ff genotype)


  • C/C genotype: high responder (bb genotype)
  • T/C genotype: moderate responder (Bb genotype)
  • T/T genotype: low responder (BB genotype)
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