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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% CI 0.50-1.50, p = 0.57) and that with carriage of the thermolabile allele was 1.06 (95% CI 0.73-1.52, p = 0.76). The odds ratios remained non-significant 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 post-hoc 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.
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
February 1999,
Arteriosclerosis, thrombosis, and vascular biology,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
March 1991,
American journal of human genetics,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
June 1996,
American journal of medical genetics,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
January 1995,
American journal of human genetics,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
March 2011,
Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
December 2004,
Psychiatric genetics,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
January 1997,
La Revue de medecine interne,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
August 2000,
Arteriosclerosis, thrombosis, and vascular biology,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
October 1996,
Circulation,
M Adams, and
P D Smith, and
D Martin, and
J R Thompson, and
D Lodwick, and
N J Samani
February 1998,
Thrombosis and haemostasis,
