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Methylenetetrahydrofolate reductase polymorphism (C-677T) and coronary artery disease
N M Malik1, P Syrris, R Schwartzman
1Medical Genetics Unit, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K.
Insights
The methylenetetrahydrofolate reductase (MTHFR) C-677T mutation was investigated as a risk factor for coronary artery disease (CAD). This study found no significant association between the MTHFR C-677T mutation and CAD in the studied UK populations.
Area of Science:
- Genetics
- Cardiovascular Disease
- Biochemistry
Background:
- Hyperhomocysteinemia is a known risk factor for atherosclerotic vascular disease.
- A common mutation (C-677T) in the methylenetetrahydrofolate reductase (MTHFR) gene results in a thermolabile enzyme.
- Enzyme homozygosity for this mutation correlates with elevated plasma homocysteine levels.
Purpose of the Study:
- To investigate the C-677T MTHFR gene mutation as a potential risk factor for coronary artery disease (CAD).
- To compare the frequency of the C-677T mutation in patients with and without angiographically proven CAD.
- To assess if the mutation's prevalence correlates with the severity of CAD, specifically arterial stenosis.
Main Methods:
- Two UK patient cohorts (London and Sheffield) were analyzed, comprising cases with CAD and control groups.
- DNA samples were genotyped using polymerase chain reaction and restriction enzyme digestion.
- Frequencies of the homozygous C-677T mutation were compared between control and CAD patient groups, including subgroups based on stenosis severity (>=99% vs. <99%).
Main Results:
- In the London sample, homozygous C-677T frequencies were 0.07 (controls), 0.09 (CAD without >=99% stenosis), and 0.10 (CAD with >=99% stenosis).
- In the Sheffield sample, frequencies were 0.08 (controls), 0.10 (CAD without >=99% stenosis), and 0.11 (CAD with >=99% stenosis).
- No statistically significant association was found between the C-677T mutation and CAD, nor with the severity of arterial stenosis in either population.
Conclusions:
- The C-677T mutation in the MTHFR gene is not a significant risk factor for coronary artery disease in the studied UK populations.
- The prevalence of the MTHFR C-677T mutation did not correlate with the degree of coronary artery stenosis.
- Further research may be warranted to explore other genetic or environmental factors contributing to CAD risk.
Abstract:
1. Many studies have shown that hyperhomocysteinaemia is a risk factor for atherosclerotic vascular disease. A mutation (C-677T) in the gene coding for the methylenetetrahydrofolate reductase (MTHFR) enzyme has been shown to produce a thermolabile form of the enzyme. Homozygosity for this mutation has been correlated with an elevated plasma homocysteine concentration. The present study aimed to determine whether this mutation was a risk factor for coronary artery disease (CAD). This was achieved by comparing the frequency of the C-677T mutation in patients with angiographically proven CAD against angiographically normal patients in two separate U.K. samples. The analysis was repeated with CAD patients split into those with >=99% stenosis of arteries and those without, to establish whether the C-677T mutation could be correlated with severity of CAD.2. Two patient groups were selected from London and Sheffield. The London group comprised 174 cases and 148 controls. The Sheffield group comprised 93 cases and 85 controls. The DNA samples of the patients were genotyped by polymerase chain reaction and restriction enzyme digestion.3. For London the homozygous C-677T frequencies were: 0.07 (controls), 0.09 (CAD without >=99% stenosis) and 0.10 (CAD with >=99% stenosis). For Sheffield the homozygous C-677T frequencies were: 0.08 (controls), 0.10 (CAD without >=99% stenosis) and 0.11 (CAD with >=99% stenosis). No association was found between the C-677T mutation and CAD in our sample geographical groups. Statistical comparison by genotype distribution for 0 VD (no vessel disease, i.e. 0% diameter reduction in all epicardial arteries) versus CAD without >=99% stenosis: London, P=0.19; Sheffield, P=0.53; 0 VD versus CAD with >=99% stenosis: London, P=0. 23; Sheffield, P=0.55.