A genetic variant (MTHFR C677T) puts half the population at increased risk of neural tube defects

May 20 2004

This finding underscores the importance of folic acid supplementation for all women of childbearing age to prevent neural tube defects.

Researchers in Ireland and the United States identified the genetic make-up (genotype) of 395 individuals born with neural tube defects (spina bifida or encephalocele) and 848 controls.

The TT (homozygous variant) form of the gene responsible for processing folate is associated with an increased risk of neural tube defects, but the team set out to investigate the possibility that the CT (heterozygous variant) form would also increase the risk of these malformations.

Both genotypes are linked to lower tissue concentrations of folate, higher levels of homocysteine (an amino acid), and lower enzyme activity than the wild CC genotype.

The CT genotype was responsible for at least as many neural tube defects in the population as the TT genotype. This is because a much greater proportion of the general population (38%) are CT compared with 10% who are TT.

The combined CT and TT genotypes account for about 26% of neural tube defects in Ireland, say the authors. Folate or folic acid is estimated to be involved in about 50-70% of these defects. Thus, up to half of the folate related neural tube defects may be explained by this single genetic variant.

Both the lower folate and higher homocysteine levels associated with CT and TT genotypes can be corrected by folic acid, explain the authors. Therefore, this study underscores the importance of public health intervention programmes of folic acid supplementation and food fortification targeted at all women of childbearing age to prevent neural tube defects.

Such intervention may also turn out to have other public health benefits, such as the prevention of heart disease, they conclude.