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Updated: Aug 9, 2026
A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
Thermolabile methylenetetrahydrofolate reductase in coronary artery disease
L A Kluijtmans1, J J Kastelein, J Lindemans
1Department of Pediatrics, University Hospital Nijmegen, The Netherlands.
Insights
The MTHFR 677C-->T mutation is linked to higher homocysteine levels. The homozygous MTHFR mutation is a significant risk factor for coronary artery disease (CAD).
Area of Science:
- Genetics and Cardiovascular Health
Background:
- Hyperhomocysteinemia is a risk factor for coronary artery disease (CAD).
- The methylenetetrahydrofolate reductase (MTHFR) gene's 677C-->T mutation is associated with elevated homocysteine.
- This mutation affects homocysteine metabolism, a key factor in cardiovascular health.
Purpose of the Study:
- To assess the frequency of the MTHFR 677C-->T mutation in CAD patients and controls.
- To investigate the association between the MTHFR mutation and serum homocysteine concentrations.
- To perform a meta-analysis to determine the risk of the homozygous MTHFR genotype for CAD.
Main Methods:
- Assessed mutation frequency in 735 CAD patients and 1250 controls.
- Studied the association between the MTHFR mutation and serum homocysteine levels.
- Conducted a meta-analysis of 8 case-control studies on thermolabile MTHFR in CAD.
Main Results:
- The homozygous MTHFR mutation occurred in 9.5% of CAD patients vs. 8.5% of controls (OR 1.21).
- Homocysteine levels were significantly elevated in both homozygous (+/+) and heterozygous (+/-) individuals compared to wild-type (-/-).
- Meta-analysis showed the homozygous mutation in 12.1% of patients vs. 10.4% of controls (OR 1.22, significant).
Conclusions:
- Both homozygous and heterozygous MTHFR genotypes lead to elevated homocysteine concentrations.
- The homozygous MTHFR 677C-->T genotype is a modest but significant risk factor for coronary artery disease (CAD).
Background:
Hyperhomocysteinemia, an independent and graded risk factor for coronary artery disease (CAD), may result from both environmental and hereditary factors. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate to methyltetrahydrofolate, the methyl donor in the remethylation of homocysteine to methionine. A 677C-->T mutation in the MTHFR gene has been associated with elevated homocysteine concentrations in homozygous (+/+) individuals.
Methods And Results:
We assessed the frequency of this common mutation in 735 CAD patients from the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering coronary-regression trial, and in 1250 population-based control subjects. Furthermore, the association between the mutation and serum homocysteine concentrations was studied. The frequency of the homozygous (+/+) mutation was 9.5% among patients versus 8.5% among control subjects, resulting in an odds ratio of 1.21 (95% confidence interval [CI], 0.87 to 1.68), relative to the (-/-) genotype. Homocysteine concentrations were significantly elevated in both (+/+) and (+/-) individuals compared with (-/-) individuals (median homocysteine levels, 15.4, 13.4, and 12.6 micromol/L, for (+/+), (+/-), and (-/-) individuals, respectively). For a summary estimation of the risk of the (+/+) genotype for CAD, we performed a meta-analysis on 8 different case-control studies on thermolabile MTHFR in CAD. In the meta-analysis, the homozygous (+/+) genotype was present in 299 of 2476 patients (12.1%) and in 257 (10.4%) of 2481 control subjects, resulting in a significant odds ratio of 1.22 (95% CI, 1.01 to 1.47) relative to the (-/-) genotype.
Conclusions:
Both the homozygous (+/+) and heterozygous (+/-) genotype result in elevated homocysteine concentrations. From our meta-analysis, we conclude that the homozygous (+/+) genotype is a modest but significant risk factor for CAD.
