G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population.

The functional consequences of the G80A RFC SNP on the expressed reduced folate carrier protein were evaluated by looking at the relationship between intake of folate, plasma folate and cellular stores of the vitamin. The effect on homocysteine was also examined. Homocysteine is a thiol that is known to be inversely associated with folate, and which is considered to be both thrombo- and athrogenic. At high levels, homocysteine may also interfere with nitric oxide mediated vasodilation, cause oxidative injury to, and proliferation of the vascular endothelium, and alter the elastic properties of the vascular wall, contributing to increased blood pressure. Participants (119; 52 male, 67 female) from a NSW retirement village were assessed. Independent of gender, the assimilation of folate from dietary sources into red cells showed a significant association for GG (r=0.399; p=0.022) and GA (r=0.564; p<0.0001) subjects, but not homozygous recessive (AA) individuals (r=0.223; p=0.236). The same genotype based pattern of significance was shown for the association between dietary folate and plasma folate (GG: r=0.524; p=0.002, GA: r=0.408; p=0.002). No genotype-related pattern of significance was shown for the association between dietary folate and homocysteine. When examined by gender, some differences were apparent; one-way ANOVA showed that genotype influenced diastolic blood pressure in males (p=0.019), while only females showed a significant correlation between dietary folate and blood pressure within specific genotypes (Systolic pressure GA: r=-0.372; p=0.025, carriage of A: r=0.-0.357; p=0.011. Diastolic pressure GA: r=-0.355; p=0.034, carriage of A: r=0.-0.310; p=0.029). The G80A RFC SNP had an impact on the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population.

Folate nutritional genetics and risk for hypertension in an elderly population sample.

BACKGROUND/AIMS: 118 elderly participants (65-90 years) were assessed for any relationship between folate, related genes and hypertension. METHODS: Six B-vitamin-related SNPs were genotyped in 80 normotensive and 38 hypertensive subjects. RESULTS: Of six polymorphisms (677C>T-MTHFR, 1298A>C-MTHFR, 80G>A-RFC, 2756A>G-MS, 66A>G- MSR, 19bpDHFR and 1561C>T-GCPII), only 677C>T-MTHFR was a significant risk for hypertension: OR 1.89; 95% CI 1.07-3.32 (chi2 p = 0.038). Additionally, hypertensive subjects had a significantly lower intake of dietary folate than normotensive individuals (p = 0.0221), although this did not markedly alter blood metabolite levels. Several significant linear associations between dietary folate and related blood metabolites were found in normotensive subjects (p < 0.001 for Hcy, red cell and serum folate) and were as predicted on an a priori basis -- generally weaker associations existed in hypertensive subjects (p < 0.05 for serum folate). This was true for data examined collectively or by genotype. Multiple-regression analysis for diastolic or systolic blood pressure showed significant interaction for gender and folate intake (p = 0.014 and 0.019, respectively). In both cases this interaction occurred only in females, with higher folate intake associated with decreased blood pressure. Regressing diastolic blood pressure and 677C>T-MTHFR genotype showed significance (males; p = 0.032) and borderline significance (all subjects). CONCLUSION: Dietary folate and 677C>T-MTHFR genotype may modify blood pressure.

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.