European Journal of Nutrition

, Volume 53, Issue 7, pp 1549–1559

MTHFR C677T genotype and cardiovascular risk in a general population without mandatory folic acid fortification

Authors

    • Research Centre for Prevention and Health, Glostrup University HospitalThe Capital Region of Denmark
  • Tea Skaaby
    • Research Centre for Prevention and Health, Glostrup University HospitalThe Capital Region of Denmark
  • Torben Jørgensen
    • Research Centre for Prevention and Health, Glostrup University HospitalThe Capital Region of Denmark
    • Faculty of Health and Medical SciencesUniversity of Copenhagen
  • Betina H. Thuesen
    • Research Centre for Prevention and Health, Glostrup University HospitalThe Capital Region of Denmark
  • Mogens Fenger
    • Department of Clinical BiochemistryCopenhagen Hvidovre University Hospital
  • Niels Grarup
    • The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of Copenhagen
  • Camilla H. Sandholt
    • The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of Copenhagen
  • Torben Hansen
    • The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of Copenhagen
    • Faculty of Health SciencesUniversity of Southern Denmark
  • Oluf Pedersen
    • The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of Copenhagen
    • Faculty of Health SciencesAarhus University
    • Hagedorn Research Institute
    • Institute of Biomedical Science, Faculty of Health and Medical SciencesUniversity of Copenhagen
  • Allan Linneberg
    • Research Centre for Prevention and Health, Glostrup University HospitalThe Capital Region of Denmark
    • Faculty of Health and Medical SciencesUniversity of Copenhagen
    • Department of Clinical Experimental ResearchGlostrup University Hospital
Original Contribution

DOI: 10.1007/s00394-014-0659-2

Cite this article as:
Husemoen, L.L.N., Skaaby, T., Jørgensen, T. et al. Eur J Nutr (2014) 53: 1549. doi:10.1007/s00394-014-0659-2

Abstract

Purpose

Meta-analyses have suggested an effect of MTHFR C677T genotype (rs1801133), a proxy for blood total homocysteine, on cardiovascular disease (CVD) in populations with low population dietary folate. The aim was to examine the association and effect modification by serum folate and vitamin B12 levels between MTHFR and CVD-related outcomes in a general population with no mandatory folic acid fortification policy.

Methods

The study population included 13,748 adults retrieved from pooling of four population-based studies conducted in Denmark. MTHFR genotype, serum folate (measured in approximately 9,356 individuals), and serum vitamin B12 (9,215 individuals), hypertension, and dyslipidemia were measured at baseline, and participants were followed for a mean of 10.5–11.7 years in central registries for diagnoses of stroke (623 incidents), ischaemic heart disease (IHD) (835 incidents), and all-cause mortality (1,272 incidents).

Results

The MTHFR genotype (TT vs. CC/CT) was not associated with hypertension [OR (95 % CI) 1.09 (0.95–1.25)], dyslipidemia [OR (95 % CI) 0.97 (0.84–1.11)], stroke [HR (95 % CI) 0.92 (0.69–1.23)], and all-cause mortality [HR (95 % CI) 0.94 (0.77–1.14)], either overall, or in participants with low serum folate or B12 status (P values for interactions 0.15–0.94). Individuals with the MTHFR TT genotype had a higher risk of IHD (HR (95 % CI) 1.38 (1.11–1.71)), but this association was not modified by folate status (P value for interaction 0.45).

Conclusions

Our results do not support a causal relationship between homocysteine and CVD. However, we cannot exclude a direct causal effect of MTHFR C677T genotype on IHD.

Keywords

HomocysteineFolateB12Cardiovascular diseaseMTHFRrs1801133

Copyright information

© Springer-Verlag Berlin Heidelberg 2014