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

Smulders, Yvo M.; Smith, Desiree E.C.; Kok, Robert M.; Teerlink, Tom; Gellekink, Henkjan; Vaes, Wouter H.J.; Stehouwer, Coen D.A.; Jakobs, Cornelis

doi:10.1016/j.jnutbio.2006.11.010

« Previous Next »The Journal of Nutritional Biochemistry
Volume 18, Issue 10 , Pages 693-699, October 2007

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

Yvo M. Smulders
- Department of Internal Medicine and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam 1007 MB, The Netherlands
- Corresponding author. Tel.: +31 20 4444307; fax: +31 20 4444313.
Desiree E.C. Smith
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam 1007 MB, The Netherlands
Robert M. Kok
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam 1007 MB, The Netherlands
Tom Teerlink
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam 1007 MB, The Netherlands
Henkjan Gellekink
- Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen 6500 HB, The Netherlands
Wouter H.J. Vaes
- BU Analytical Research, TNO Quality of Life, Zeist 3700 AJ, The Netherlands
Coen D.A. Stehouwer
- Department of Internal Medicine, University Hospital Maastricht and Maastricht University, Maastricht 6202 AZ, The Netherlands
Cornelis Jakobs
- Department of Clinical Chemistry, VU University Medical Center, Amsterdam 1007 MB, The Netherlands

Received 7 August 2006; received in revised form 9 November 2006; accepted 9 November 2006. published online 06 April 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.

Keywords: Folate, B vitamins, Methylenetetrahydrofolate reductase (MTHFR), Mass spectrometry, Red blood cell