Title
Red blood cell folate vitamer distribution in healthy subjects is determined by the methylenetetrahydrofolate reductase C677T polymorphism and by the total folate status
Author
Smulders, Y.M.
Smith, D.E.C.
Kok, R.M.
Teerlink, T.
Gellekink, H.
Vaes, W.H.J.
Stehouwer, C.D.A.
Jakobs, C.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
Background: Red blood cells (RBCs) represent a storage pool for folate. In contrast to plasma, RBC folate can appear in different biochemical isoforms. So far, only the methylenetetrahydrofolate reductase (MTHFR) 677 TT genotype has been identified as a determinant of RBC folate vitamer distribution. Objective: The purpose of this study is to identify clinical and biochemical determinants of RBC folate vitamer distribution in healthy subjects. Design: In an observational study, 109 subjects, aged 18 to 65 years, were studied. Red blood cell folate vitamers were analyzed using a liquid chromatography-tandem mass spectrometry method. Other variables recorded included vitamin B2, B6 and B12 status, homocysteine, plasma and RBC S-adenosylhomocysteine and S-adenosylmethionine, renal function and the MTHFR C677T polymorphism. Results: The MTHFR C677T genotype was the dominant determinant of nonmethylfolate accumulation. The median (range) nonmethylfolate/total folate ratio was 0.58% (0-12.2%) in the MTHFR CC group (n=55), 0.99% (0-14.3%) in the CT group (n=39) and 30.3% (5.7-73.3%) in the TT genotype group (n=15), P<.001. The 95th percentile for the nonmethylfolate/total folate ratio was 2.8% for the CC group, 9.1% for the CT group and 73.3% for the TT group. In the CC and CT genotype subjects, the T-allele and total folate status were positively and independently correlated with nonmethylfolate accumulation, but the degree of nonmethylfolate accumulation in these subjects was usually minor compared with those with the TT genotype. None of the other studied variables was associated with nonmethylfolate accumulation. Conclusions: The MTHFR C677T genotype is the dominant determinant of nonmethylfolate accumulation in RBCs. In addition, high total folate status may contribute to minor to moderate nonmethylfolate accumulation in MTHFR CC and CT subjects. © 2007 Elsevier Inc. All rights reserved.
Subject
Biology
Analytical research
B vitamins
Folate
Mass spectrometry
Methylenetetrahydrofolate reductase (MTHFR)
Red blood cell
5,10 methylenetetrahydrofolate reductase (FADH2)
cyanocobalamin
folic acid
homocysteine
pyridoxine
riboflavin
s adenosylhomocysteine
s adenosylmethionine
adult
aged
allele
article
controlled study
enzyme polymorphism
erythrocyte
female
genotype
human
kidney function
liquid chromatography
male
normal human
plasma
tandem mass spectrometry
Adolescent
Adult
Erythrocytes
Female
Folic Acid
Humans
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Polymorphism, Genetic
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http://resolver.tudelft.nl/uuid:d06500e3-3552-47d8-a6f6-671e0d0eb16e
DOI
https://doi.org/10.1016/j.jnutbio.2006.11.010
TNO identifier
240213
ISSN
0955-2863
Source
Journal of Nutritional Biochemistry, 18 (10), 693-699
Document type
article