Elsevier

Clinical Biochemistry

Volume 41, Issue 3, February 2008, Pages 174-176
Clinical Biochemistry

Distinct association of SLC19A1 polymorphism − 43T>C with red cell folate levels and of MTHFR polymorphism 677C>T with plasma folate levels

https://doi.org/10.1016/j.clinbiochem.2007.11.006Get rights and content

Abstract

Objectives:

The role of SLC19A1 43T>C, MTHFR 677C>T and MS 2756A>G polymorphisms on red cell and plasma folate levels.

Design and methods:

Genotype analysis of the three polymorphisms. Red cell and plasma folate measurements in 64 patients with coronary artery disease.

Results:

The non-wild type allele of SLC19A1 polymorphism − 43T>C was associated with low red cell folate levels and the non-wild type allele of MTHFR polymorphism 677C>T with low plasma folate levels.

Conclusion:

SLC19A1 and MTHFR genes are differently associated with red cell and plasma folate levels.

Introduction

Folate-mediated one-carbon transfers represent important biochemical reactions that are essential for the synthesis of various nucleic acids (purine, thymidine) and amino acids (methionine, histidine, serine) [1]. Therefore, folates are essential for normal cell growth, maturation, survival and proliferation. However, the metabolic pathway of folate transport into cell and its subsequent metabolism involves many proteins. The insertion of these compounds into cell employs primarily the reduced folate carrier (RFC protein, SLC19A1 gene), while two enzymes have mainly been studied regarding to folate metabolism; the methylenetetrahydrofolate reductase (MTHFR) and the methionine synthase (MS) [1], [2], [3].

The MTHFR 677C>T (A222V) and the MS 2756A>G (D919G) polymorphisms have been associated with increased plasma homocysteine and decreased plasma folate levels [2], [3]. Specifically, the MTHFR polymorphism 677C>T results in a thermolabile enzyme with decreased activity [4], while the effect of 2756A>G variant on MS enzyme activity remains unknown [3]. In addition, their role in coronary artery disease (CAD) remains controversial [2], [3].

We have previously reported that the low red cell folate levels, as opposed to low plasma folate levels, are associated with acute coronary events in CAD patients and the non-wild type allele of SLC19A1 gene polymorphism − 43T>C is related to decreased RFC protein expression levels [5], [6].

In the present study, we investigated the role of SLC19A1 − 43T>C, MTHFR 677C>T and MS 2756A>G polymorphisms on red cell and plasma folate levels in CAD patients.

Section snippets

Patients and methods

Genomic DNA was extracted from peripheral blood lymphocytes according to the standard salt extraction procedure from 64 patients with CAD (60 males, mean age: 53.9 years), diagnosed with coronary angiography. Data concerning red cell and plasma folate concentrations had been collected during their clinical follow-up. All subjects gave informed written consent and the local ethics committee granted approval.

Polymorphisms − 43T>C (SLC19A1), 677C>T (MTHFR) and 2756A>G (MS) were amplified using

Results

The distribution of genotypes of the three studied polymorphisms, the red cell and plasma folate levels are shown in Table 1. Polymorphisms − 43T>C (SLC19A1) and 677C>T (MTHFR) were in Hardy–Weinberg equilibrium. Polymorphism 2756A>G (MS) was not in Hardy–Weinberg equilibrium since the 2756GG genotype was not found in our study group. For this reason, any association of MS 2756A>G variant with red cell and plasma folate level would be doubtful, as it was revealed by the low power of the

Discussion

The present study demonstrated that SLC19A1 polymorphism − 43T>C is related to red cell folate levels; homozygous carriers of the non-wild type SLC19A1 allele − 43C have significantly lower red cell folate levels compared to homozygous carriers of the wild type allele − 43T. Furthermore, in the present study, MTHFR polymorphism 677C>T was found to be related to plasma folate levels as previously reported [2]; significantly lower plasma folate levels were found in the homozygous carriers of the

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