As a toddler, we learn the song “Head and Shoulders, Knees and Toes, Eyes, Ears, Mouth and Nose“. We recognize people by their external characteristics – sex, voice, eye color, hair, and body size. Soon we learn that all people don’t all behave the same. It shouldn’t be surprising to realize that people differ on the inside too!
Genetic testing is frequently proposed as a means to identify risk for developing cancer or other inherited mutations associated with disease.
Folate [or folic acid the form used in food fortification and dietary supplements] is a B vitamin which is an essential to make nucleic acids (DNA & RNA), methionine regeneration (amino acid metabolism), and one-carbon units required for metabolism (Bailey & Gregory, 1999).
The methylene tetrahydrofolate reductase (MTHFR) gene encodes for an enzyme, MTHFR, which is essential for folate metabolism. Because of a single amino acid substitution (valine for alanine), 3 common MTFHR polymorphisms are found in the human population: MTHFR 677 CC, MTHFR 677 CT, MTHFR 677 TT (Wang et al., 2016).
Shane et al (2018) screened the entire human genome for common genetic polymorphisms that influence folate-status biomarkers in 2,232 young, healthy Irish university students. They report mean red blood cell (RBC) folate concentrations for women and men of 1058 and 1,099 nmol/L, respectively. RBC folate concentrations were not distributed normally; presumably because they were higher in the 23% of the population using dietary supplements containing folic acid. The authors report:
Our studies clearly indicate that the MTHFR 677C→T (rs1801133) variant is the major genetic modifier of folate status biomarkers and may be the only significant modifier of serum (plasma) and red blood cell folate concentrations, at least in young, healthy adults in the Irish population.
Shane et al (2018) also write:
The T allele of MTHFR 677 causes decreases in both serum and red blood cell folate, the latter being a proxy for tissue folate, which would indicate an impairment in folate status.
But this is the clincher from their paper:
Because the poorer folate status caused by this variant is reflected in the changes in the concentrations of these biomarkers for folate status, there does not appear to be any added benefit in genotyping subjects for this variant (emphasis added) when interpreting folate status through the use of these biomarkers. Carriers of the T allele are also responsive to folate intake (31), which indicates that a T allele–dependent low folate status is responsive to treatment, also making genetic testing unnecessary.
The World Health Organization (WHO) recommendation for countries is that women of reproductive age should maintain RBC folate concentrations >906 nmol/L to achieve the greatest reduction in NTDs.
The US and Canadian governments mandated folic acid fortification of flour in 1998. According to the CDC, this legislation has prevented approximately 1,300 babies being born with NTDs in the US annually. Since mandatory fortification, mean RBC concentrations have risen significantly.
Nevertheless, approximately 33% of women of childbearing age may still not achieve WHO recommended RBC folate concentrations.
Genetic testing for MTHFR polymorphisms isn’t necessary. A simple blood test for RBC folate concentration will suffice to determine if folate status is adequate.