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Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and

Nader Khandanpour1, Gavin Willis, Felicity J Meyer

  • 1Department of Vascular Surgery, Norfolk and Norwich University Hospital, Norwich, England.

Journal of Vascular Surgery
|January 23, 2009
PubMed

Insights

The methylenetetrahydrofolate reductase (MTHFR) C677T gene variant is linked to higher homocysteine levels. This genetic factor increases the risk of developing peripheral arterial disease (PAD).

Area of Science:

  • Genetics
  • Cardiovascular Disease
  • Metabolic Disorders

Background:

  • Hyperhomocysteinemia is a known risk factor for peripheral arterial disease (PAD).
  • Genetic variations, specifically polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, influence homocysteine metabolism and can lead to elevated homocysteine levels.
  • Understanding the role of MTHFR C677T polymorphism in PAD development is crucial for risk assessment.

Purpose of the Study:

  • To investigate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of peripheral arterial disease (PAD).
  • To analyze the impact of MTHFR C677T genotype on plasma homocysteine levels in PAD patients.
  • To synthesize findings with existing literature through a meta-analysis.

Main Methods:

  • A case-control study comparing MTHFR C677T allele frequencies in 133 PAD patients and 457 healthy controls.
  • Cross-sectional analysis of plasma total homocysteine levels in relation to MTHFR genotypes.
  • Systematic literature search (Medline, Embase, Cochrane) and meta-analysis of relevant studies published up to March 2008.

Main Results:

  • The T allele and TT genotype of MTHFR C677T polymorphism showed an increased odds ratio for PAD (1.18 and 1.99, respectively).
  • Individuals with the MTHFR C677T TT genotype had significantly higher plasma total homocysteine concentrations (OR 2.82).
  • A meta-analysis of 9 studies, including this one, indicated that homozygous MTHFR C677T genotype is associated with increased PAD risk (pooled OR 1.36).

Conclusions:

  • A significant association exists between elevated homocysteine levels, the MTHFR C677T TT genotype, and the risk of peripheral arterial disease.
  • The MTHFR C677T polymorphism is a relevant genetic factor contributing to PAD development.
  • These findings support the role of homocysteine metabolism in PAD pathogenesis.
Abstract

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