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Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms

C Bickel1, R B Schnabel2, E Zengin2

  • 1Department of Internal Medicine, Federal Armed Forces Central Hospital, Koblenz, Germany.

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD
|October 25, 2016
PubMed

Insights

Single nucleotide polymorphisms (SNPs) in the MTHFR enzyme affect homocysteine levels but do not influence cardiovascular event rates in coronary artery disease (CAD) patients. Other SNPs studied also showed no impact on prognosis.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Biochemistry

Background:

  • The association between homocysteine metabolism enzyme single nucleotide polymorphisms (SNPs) and cardiovascular (CV) events in coronary artery disease (CAD) patients is debated.
  • Elevated homocysteine levels are linked to increased CV risk.

Purpose of the Study:

  • To investigate whether specific SNPs in homocysteine metabolism enzymes impact CV event rates in CAD patients.
  • To determine the relationship between MTHFR, MS, and CBS gene polymorphisms and homocysteine levels and CV outcomes.

Main Methods:

  • Analysis of 1126 CAD patients and 332 controls from the AtheroGene study.
  • Genotyping for methylenetetrahydrofolate reductase (MTHFR-C667T), methionine synthase (MS-D919G), and cystathionine beta-synthase (CBS-I278T) SNPs.
  • Follow-up for a composite endpoint of CV death, stroke, and non-fatal myocardial infarction over a median of 6.4 years.

Main Results:

  • Higher homocysteine levels correlated with increased CV event rates in CAD patients (p < 0.001).
  • Homocysteine was an independent predictor of CV events (HR 6.5, p < 0.001).
  • Homozygous MTHFR SNPs significantly increased homocysteine levels in both CAD patients and controls (p < 0.001), but MS and CBS SNPs did not.
  • None of the investigated SNPs (MTHFR, MS, CBS) were associated with an increased rate of CV events.

Conclusions:

  • Homocysteine levels are a significant predictor of CV events.
  • MTHFR gene polymorphisms influence homocysteine levels but do not affect long-term CV prognosis in CAD patients.
  • SNPs in MS and CBS enzymes do not significantly alter homocysteine levels or CV event rates.
Abstract

Keywords:
Coronary artery diseaseHomocysteineOutcomeSingle nucleotide polymorphisms

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