Original Contribution

European Journal of Nutrition

, Volume 53, Issue 7, pp 1549-1559

First online:

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

  • Lise Lotte N. HusemoenAffiliated withResearch Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark Email author 
  • , Tea SkaabyAffiliated withResearch Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark
  • , Torben JørgensenAffiliated withResearch Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of DenmarkFaculty of Health and Medical Sciences, University of Copenhagen
  • , Betina H. ThuesenAffiliated withResearch Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of Denmark
  • , Mogens FengerAffiliated withDepartment of Clinical Biochemistry, Copenhagen Hvidovre University Hospital
  • , Niels GrarupAffiliated withThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
  • , Camilla H. SandholtAffiliated withThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
  • , Torben HansenAffiliated withThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenFaculty of Health Sciences, University of Southern Denmark
  • , Oluf PedersenAffiliated withThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenFaculty of Health Sciences, Aarhus UniversityHagedorn Research InstituteInstitute of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen
    • , Allan LinnebergAffiliated withResearch Centre for Prevention and Health, Glostrup University Hospital, The Capital Region of DenmarkFaculty of Health and Medical Sciences, University of CopenhagenDepartment of Clinical Experimental Research, Glostrup University Hospital

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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.

Keywords

Homocysteine Folate B12 Cardiovascular disease MTHFR rs1801133