Author
KALMBACH, RENEE - HNRCA AT TUFTS UNIVERSITY | |
CHOUMENKOVITCH, SILVINA - HNRCA AT TUFTS UNIVERSITY | |
Jacques, Paul | |
D'AGOSTINO, RALPH - BOSTON UNIVERSITY | |
TROEN, ARON - HNRCA AT TUFTS UNIVERSITY | |
Selhub, Jacob |
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only Publication Acceptance Date: 12/1/2007 Publication Date: 4/4/2008 Citation: Kalmbach, R., Choumenkovitch, S., Jacques, P., D'Agostino, R.B., Troen, A., Selhub, J. 2008. Relationship between the 19 base pair deletion polymorphism in DHFR and unmetabolized folic and in plasma and RBC folate. Federation of American Societies for Experimental Biology Journal. 22:296.4. Interpretive Summary: Technical Abstract: Background: A 19 base pair (bp) deletion allele of dihydrofolate reductase (DHFR), an enzyme that makes folic acid metabolically active and reduces dihydrofolate to tetrahydrofolate to stimulate folate turnover, has been implicated in folate related health outcomes. Objective: Examine the effect of the -19 bp allele on measures of folate status and to determine if folic acid intake modifies any relations between the DHFR polymorphism and plasma folate, RBC folate, homocysteine, and unmetabolized folic acid concentrations. Methods: DHFR genotype was determined in 1215 subjects from the Framingham Offspring Study. Results: The -19 bp allele was not associated with any measures of folate status, but there were significant interactions between genotype and folic acid intake with RBC folate and prevalence of unmetabolized folic acid concentrations >/= 85%, suggestive of high unmetabolized folic acid (P for interactions = 0.01 and 0.02 respectively). At high folic acid intake (>500ug) the prevalence of high unmetabolized folic acid was significantly greater in the -/- genotype (45.8%) compared to the +/- (21.7%) and +/+ (24.5%) (P =0.02 for all comparisons). At low folic acid intake (<250ug), those with the -/- genotype had significantly lower RBC folate (918.4 ug/L) compared to the +/+ genotype (1068.9 ug/L)(P =0.02). Conclusions: The DHFR 19 bp deletion allele affects RBC folate and unmetabolized folic acid status through an interaction with folic acid intake. |