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Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611
2To whom correspondence and reprint requests should be addressed.
A common genetic polymorphism results from a C
T substitution in the
gene encoding methylenetetrahydrofolate reductase (MTHFR), the enzyme
that produces 5-methyltetrahydrofolate (5-methyl-THF) required for the
conversion of homocysteine to methionine. In individuals with the T/T
genotype (T/T), functional metabolic effects include changes in
one-carbon folate derivatives, elevations in plasma homocysteine
and differences in response to folic acid supplementation compared with
normal (C/C) or heterozygous (C/T) genotypes. The metabolic changes
associated with the T/T genotype are postulated to modify risk for
chronic disease (e.g., vascular disease and cancer) and neural tube
defects (NTD) when accompanied by folate deficiency. The modulation of
these metabolic abnormalities by increasing folate intake suggests that
folate requirements may be different in affected individuals (T/T)
relative to normal (C/C) or heterozygous (C/T) individuals. The complex
interaction between this common genetic polymorphism of MTHFR and
folate intake is the focus of intense investigation.
KEY WORDS: • folate • MTHFR polymorphism • homocysteine • vascular disease • cancer • neural tube defects
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