Key Findings from Recent Birth Defects and Pediatric Genetics Branch Projects

MTHFR Gene Variants and Birth Defects

CDC scientists reviewed epidemiologic information on the MTHFR gene variants and birth defects.

• MTHFR (5,10 methylenetetrahydrofolate reductase) is an enzyme of the metabolism of folate and homocysteine and is involved in substrate methylation and in the synthesis of nucleotides. The gene is on chromosome 1p36.3.
    

• In addition to rare mutations, two common gene variants of MTHFR -- the C677T and the 1298C variants -- have been described in many populations.
    

• The frequency of the C677T allele varies internationally. The frequency of C677T homozygotes is 20 percent or more among Italians and some Hispanic groups in the United States and Latin America, but it is only 1 percent among some groups in Africa.
    

• Homozygosity for the C677T is approximately twice as common among children with spina bifida and their mothers than among unaffected people. Whether this association is causal, however, is unclear.
    

• The risk for spina bifida associated with C677T homozygosity may change depending on environmental factors. The risk may be lower if mothers take multivitamins before and during early pregnancy, or if blood levels of folate are not low. Other genes might also play a role. These interactions need to be studied further.
    

• The link between MTHFR variants and other birth defects has been much less studied. Studies on oral clefts, Down syndrome, and fetal anticonvulsant syndrome have yielded conflicting results or are yet unreplicated.
    

• Population testing for MTHFR gene variants is not done nor advocated.

Results published in: American Journal of Epidemiology 2000;151:862-77.  (Abstract)