Red blood cell folate vitamer distribution in healthy subjects is determined by the methylenetetrahydrofolate reductase C677T polymorphism and by the total folate status.
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.


METHODS
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 B(2), B(6) and B(12) 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.
Smulders
Yvo M
YM
Department of Internal Medicine and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam 1007 MB, The Netherlands. y.smulders@vumc.nl
Smith
Desiree E C
DE
Kok
Robert M
RM
Teerlink
Tom
T
Gellekink
Henkjan
H
Vaes
Wouter H J
WH
Stehouwer
Coen D A
CD
Jakobs
Cornelis
C
D000293:Adolescent; D000328:Adult; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)