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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #226964

Title: Relationship between the 19 base pair deletion polymorphism in DHFR and unmetabolized folic and in plasma and RBC folate

Author
item KALMBACH, RENEE - HNRCA AT TUFTS UNIVERSITY
item CHOUMENKOVITCH, SILVINA - HNRCA AT TUFTS UNIVERSITY
item Jacques, Paul
item D'AGOSTINO, RALPH - BOSTON UNIVERSITY
item TROEN, ARON - HNRCA AT TUFTS UNIVERSITY
item 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.