Rare allelic variants determine folate status in an unsupplemented European population

0381453 - ÚI 2013 RIV US eng J - Journal Article
Pavlíková, Markéta - Sokolová, J. - Janošíková, B. - Melenovská, P. - Krupková, L. - Zvárová, Jana - Kožich, V.
Rare allelic variants determine folate status in an unsupplemented European population.
Journal of Nutrition. Roč. 142, č. 8 (2012), s. 1403-1409. ISSN 0022-3166. E-ISSN 1541-6100
R&D Projects: GA MZd(CZ) NS10036
Institutional research plan: CEZ:AV0Z10300504
Keywords : glutamate-carboxypeptidase-ii * coronary-artery-disease * one-carbon metabolism * methylenetetrahydrofolate reductase * homocysteine concentrations * genetic-determinants * common mutation * serum folate * polymorphisms * prevalence
Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition
Impact factor: 4.196, year: 2012

The role of folates as coenzymes in 1-carbon metabolism and the clinical consequences of disturbed folate metabolism are widely known. Folate status is a complex trait determined by both exogenous and endogenous factors. This study analyzed the association between 12 genetic variants and folate status in a Czech population with no folate fortification program. These 12 genetic variants were selected from 56 variant alleles found by resequencing the coding sequences and adjacent intronic regions of 6 candidate genes involved in folate metabolism or transport (FOLR1, FOLR2, FOLR3, MTHFR, PCFT, and RFC) from 29 individuals with low plasma and erythrocyte folate concentrations. Regression analyses of a cohort of 511 Czech controls not taking folate supplements revealed that only 2 variants in the MTHFR gene were associated with altered folate concentrations in plasma and/or erythrocytes. In our previous study, we observed that the common variant MTHFR c.665C > T (known as c.677C > T; p.A222V) was associated with decreased plasma folate concentrations. In the present study, we show in addition that the rare variant MTHFR c.1958C > T (p.T653M) is associated with significantly increased erythrocyte folate concentrations (P = 0.02). Multivariate regression analysis revealed that this uncommon variant, which is present in 2% of Czech control chromosomes, explains 0.9% of the total variability of erythrocyte folate concentrations; the magnitude of this effect size was comparable with that of the common MTHFR c.665C > T variant. This result indicates that the rare genetic variants may determine folate status to a similar extent as the common allelic variant. J. Nutr. 142: 1403-1409, 2012.
Permanent Link: http://hdl.handle.net/11104/0211918