Preliminary evidence for genetic selection of 677T-MTHFR by natural annual cycle of folate abundance

Background/Aims: Folic acid mediates transfer of one-carbon units into methionine and DNA-thymine biosynthesis. Discretionary and mandatory use of synthetic folic acid (SFA) to reduce spina bifida is on the increase. We show that historically, the seasonal cycle of abundance of folate-rich foods may have regulated embryo viability by acting as a selection factor for a significant polymorphism within a gene encoding 5,10-methylenetetrahydrofolate reductase (677C→T-MTHFR). Methods: Blood was collected from 150 UK and 118 Australian subjects born prior to discretionary or mandatory use of SFA. 677C→T-MTHFR genotype was determined using PCR. Results: The highest prevalence for 677T-MTHFR occurred 9 months post-harvest in UK subjects and was significantly higher at this time of year (July-Sept.) compared with Jan.-Mar. (OR = 2.0, 95% CI 1.03-3.87, p = 0.039) and Oct.-Dec. (OR = 2.2, 95% CI 1.12-4.31, p = 0.021). This effect was not detected in an Australian population subject to more moderate seasonality. Conclusions: Dietary folate may confer significant genetic buffering within populations dependent upon seasonal food sources that modify an individual's vitamin status at the time of conception.