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Q J Med 1996; 89: 437-444
© 1996 Association of Physicians
Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk factor for myocardial infarction
1 Department of Cardiology, University of Leicester Leicester, UK 2 Department of Medicine, University of Leicester Leicester, UK 3 Department of Ophthalmology, University of Leicester Leicester, UK
Address correspondence to Dr N.J. Samani, Department of Cardiology, Clinical Sciences Wing, Glenfield Hospital, Groby Road, Leicester LE3 9QP
Received 2 January 1996 and in revised form 21 February 1996
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Abstract |
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Hyperhomocyst(e)inemia is associated with an increased risk of coronary artery disease and myocardial infarction. Both genetic and environmental factors influence the plasma level of homocysteine. One of the metabolic pathways for homocysteine involves the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates the conversion of homocysteine to methionine. A thermolabile variant of MTHFR is associated with reduced enzyme activity and increased plasma homocysteine levels. Recently, the cause of this variant of MTFHR has been identified as a single base change altering an alanine to a valine residue in the protein. Using a PCR-based assay to distinguish the normal and thermolabile variants of MTHFR in this study, we investigated whether the thermolabile variant is a genetic risk factor for myocardial infarction. In a study of 532 subjects (310 myocardial infarction patients and 222 population-based controls), we found no difference in either MTHFR genotype distribution (p = 0.57) or allele frequencies (p = 0.68) between cases and controls. The allele frequencies of the thermolabile variant were 0.34 and 0.35 in cases and controls, respectively. The age- and sex-stratified odds ratio for risk of myocardial infarction associated with homozygosity for the thermolabile variant was 0.85 (95% Cl 0.50–1.50, p = 0.57) and that with carriage of the thermolabile allele was 1.06 (95% Cl 0.73–1.52, p = 0.76). The odds ratios remained nonsignificant when restricted to young subjects (< 60 years) or males, and were not influenced by several other risk factors for myocardial infarction considered either singly or in combination. Interestingly, in both cases and controls, there was a trend toward a higher prevalence of hypertension in subjects carrying the normal allele, although as this is a posthoc finding it needs to be interpreted with caution. The thermolabile variant of MTHFR is not a major risk factor for myocardial infarction and is unlikely to explain a significant proportion of the reported association of hyperhomocyst(e)inemia with coronary artery disease.
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