CDC scientists reviewed epidemiologic information on the
MTHFR gene variants and birth defects.
(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)
Date:
June 17, 2005
Content source: National Center on Birth Defects and Developmental
Disabilities
