The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake.
BACKGROUND
Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Common genetic variation within DHFR is restricted to the noncoding regions, and previous studies have focused on a 19 bp deletion/insertion polymorphism (rs70991108) within intron 1. Reports of an association between this polymorphism and blood folate biomarker concentrations are conflicting.


OBJECTIVE
In this study, we evaluated whether the DHFR 19 bp deletion/insertion polymorphism affects circulating folate biomarkers in, to our knowledge, the largest cohort to address this question to date.


METHODS
Healthy young Irish individuals (n = 2507) between 19 and 36 y of age were recruited between February 2003 and February 2004. Folic acid intake from supplements and fortified foods was assessed with the use of a customized food intake questionnaire. Concentrations of serum folate and vitamin B-12, red blood cell (RBC) folate, and plasma total homocysteine (tHcy) were measured. Data were analyzed with the use of linear regression models.


RESULTS
Folic acid intake was positively associated with serum (P < 0.0001) and RBC (P = 0.0005) folate concentration and was inversely associated with plasma tHcy (P = 0.001) as expected. The DHFR 19 bp polymorphism was not significantly associated with either serum (P = 0.82) or RBC (P = 0.21) folate, or plasma tHcy (P = 0.20), even in those within the highest quintile of folic acid intake (>326 μg folic acid/d; P = 0.96). A nonsignificant trend toward lower RBC folate by genotype (P = 0.09) was observed in the lowest folic acid intake quintile (0-51 μg/d).


CONCLUSIONS
In this cohort of healthy young individuals, the DHFR 19 bp deletion allele did not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect from this polymorphism on blood folate concentrations.
Nutritional Genomics Group, School of Biotechnology, Dublin City University, Dublin, Ireland;
Mari
M
Ozaki
Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland;
Anne M
AM
Molloy
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and.
James L
JL
Mills
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and.
Ruzong
R
Fan
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and.
Yifan
Y
Wang
Institute of Food and Health, University College Dublin, Dublin, Ireland; and.
Eileen R
ER
Gibney
University of California, Berkeley, Berkeley, CA.
Barry
B
Shane
Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD;
Lawrence C
LC
Brody
Nutritional Genomics Group, School of Biotechnology, Dublin City University, Dublin, Ireland; anne.parle-mcdermott@dcu.ie.
Anne
A
Parle-McDermott
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D005494:Folic Acid Deficiency / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D005527:Food, Fortified; D056726:Genetic Association Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007438:Introns; D007494:Ireland; D008297:Male; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D014805:Vitamin B 12
19 bp polymorphism; DHFR; folic acid; homocysteine; plasma folate; red cell folate; rs70991108