The influence of 5,10 methylenetetrahydrofolate reductase genotypes on enzyme activity in placental tissue

Objective To study the effects of heterozygosity and homozygosity for the C677T mutation of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene on the activity of this enzyme in placental tissue from pregnancies not affected by neural tube defect. Design Placental tissue was genotyped for the C677T variants of MTHFR. Total enzyme activity and residual activity after heating to 46 degrees C for 5 minutes was then measured. Setting A teaching hospital. Sample Placental samples (n = 200), one from each of 200 uncomplicated term deliveries. Main outcome measures Total and residual enzyme activity for MTHFR. Results Placentae heterozygous for the C677T mutation of the MTHFR gene had significantly lower total enzyme activity than those without the mutation; the lowest activity occurred in homozygotes for the mutation. The same pattern was seen in relation to enzyme activity after heating. Conclusion This study demonstrates that reduced enzyme activity is associated with the C677T variant of MTHFR in placental tissue. This is an important metabolic step in folic acid metabolism and pro-(sic).