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Homocysteine-reducing B vitamins and ischemic heart disease: a separate-sample Mendelian randomization analysis

J V Zhao1, C M Schooling1,2

  • 1School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

European Journal of Clinical Nutrition
|December 1, 2016
PubMed

Insights

Genetically determined homocysteine, folate, and vitamin B12 levels were not associated with coronary artery disease risk. These findings challenge observational links between homocysteine and cardiovascular health.

Area of Science:

  • Cardiovascular Genetics
  • Nutritional Epidemiology
  • Metabolic Research

Background:

  • Observational studies link higher homocysteine to increased ischemic heart disease (IHD) risk and unhealthy lipids.
  • Folate and vitamin B12, which lower homocysteine, are associated with reduced IHD risk and improved lipid profiles.
  • Randomized controlled trials have not demonstrated benefits of folate and vitamin B12 for IHD.

Purpose of the Study:

  • To clarify the role of genetically determined homocysteine, folate, and vitamin B12 in IHD and lipid profiles.
  • To assess the causal relationship between these factors and cardiovascular disease, independent of observational biases.

Main Methods:

  • Mendelian randomization analysis using single-nucleotide polymorphisms (SNPs) as genetic instruments.
  • Utilized large-scale genetic data from CARDIoGRAMplusC4D (coronary artery disease/myocardial infarction) and the Global Lipids Genetics Consortium.

Main Results:

  • Genetically determined homocysteine was not associated with coronary artery disease/myocardial infarction (CAD/MI).
  • Folate and vitamin B12 levels, determined by genetic variants, showed no significant association with CAD/MI.
  • Vitamin B12 showed a potential association with unfavorable lipid profiles, specifically higher low-density lipoprotein cholesterol and triglycerides.

Conclusions:

  • The study does not support the observational association between homocysteine and CAD/MI.
  • Findings do not corroborate the protective associations of folate and vitamin B12 with CAD/MI.
  • Vitamin B12 may influence lipid profiles, warranting further investigation.
Abstract

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