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

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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.

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Acknowledgments

The present study was supported by grants from the Health Insurance Foundation (Grant No. 2010 B 131), and the Danish Agency for Science Technology and Innovation (Grant No. 2101-06-0065). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). The study was partially funded by the Lundbeck Foundation (The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp), www.lucamp.org).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Research Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark, Nordre Ringvej 57, 2600, Glostrup, Denmark

    Lise Lotte N. Husemoen, Tea Skaaby, Torben Jørgensen, Betina H. Thuesen & Allan Linneberg

  2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Torben Jørgensen & Allan Linneberg

  3. Department of Clinical Biochemistry, Copenhagen Hvidovre University Hospital, Hvidovre, Denmark

    Mogens Fenger

  4. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Niels Grarup, Camilla H. Sandholt, Torben Hansen & Oluf Pedersen

  5. Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

    Torben Hansen

  6. Faculty of Health Sciences, Aarhus University, Aarhus, Denmark

    Oluf Pedersen

  7. Hagedorn Research Institute, Gentofte, Denmark

    Oluf Pedersen

  8. Institute of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Oluf Pedersen

  9. Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark

    Allan Linneberg

Authors
  1. Lise Lotte N. Husemoen
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  2. Tea Skaaby
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  10. Allan Linneberg
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Corresponding author

Correspondence to Lise Lotte N. Husemoen.

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Husemoen, L.L.N., Skaaby, T., Jørgensen, T. et al. MTHFR C677T genotype and cardiovascular risk in a general population without mandatory folic acid fortification. Eur J Nutr 53, 1549–1559 (2014). https://doi.org/10.1007/s00394-014-0659-2

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  • DOI: https://doi.org/10.1007/s00394-014-0659-2

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