MTHFR Genotypes

In the case of the MTHFR 677C→T polymorphism, people may have two copies of the “C” allele; two copies of the “T” allele; or one copy of each. These combinations are known as “genotypes.”  The CC genotype (meaning both copies of the gene contain the “C” allele) is referred to as “homozygous normal,” and the TT genotype as the “homozygous variant.”  The CT genotype is described as “heterozygous.”

Possible MTHFR 677 alleles

677C

677T

677C

Homozygous “normal” 
CC genotype

heterozygous CT
genotype

677T

heterozygous CT
genotype

homozygous “variant”
TT genotype

As discussed previously, the T allele creates an enzyme that is less efficient.  The functionality of the MTHFR enzyme is about half as efficient in women with two T alleles (TT genotype) compared to women with two C alleles (CC genotype). Compared to women with the CC genotype, women with the TT genotype are at higher risk of having a child with a NTD especially if their folate status is low.  However, only about 15% of NTD-affected pregnancies are attributed to the MTHFR TT genotype. There are multiple genetic and environmental factors that contribute to NTD risk, which is why all women of reproductive potential are at risk regardless of which MTHFR genotype they have.