(Stroke. 1999;30:969-973.)
© 1999 American Heart Association, Inc.
Original Contributions |
Plasma Homocyst(e)ine Concentration, But Not MTHFR Genotype, Is Associated With Variation in Carotid Plaque Area
From Robarts Research Institute, University of Western Ontario, London, Ontario, Canada (J.D.S., D.F., R.A.H.); Oregon Regional Primate Research Center, Beaverton, Ore (M.R.M.); London Health Sciences Centre, London, Ontario, Canada (P.A.B.); and the Section of Cardiology, Baylor College of Medicine, Houston, Tex (A.J.M.).
Correspondence to Robert A. Hegele, MD, Blackburn Cardiovascular Genetics Laboratory, John P. Robarts Research Institute, 406-100 Perth Drive, London, Ontario, Canada N6A 5K8. E-mail robert.hegele{at}rri.on.ca
Background and Purpose—Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR). We sought to determine whether plasma H(e) concentration or MTHFR genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis.
Methods—In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2-dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and MTHFR genotypes.
Results—We found that the frequency of the MTHFR 677T allele was 0.363 in this sample. Mean plasma H(e) concentration was significantly higher in 677T/T homozygotes than in 677T/C heterozygotes and 677C/C homozygotes (17.1±13.7 versus 13.5±6.1 versus 12.6±5.9 µmol/L, respectively, P<0.001). Analysis of variance showed that CPA was significantly associated with age, sex, smoking, diabetes, hypertension, and hyperlipidemia (each P<0.05). When plasma H(e) concentration was included in the model, it was significantly associated with CPA (P<0.05). However, when the MTHFR genotype was included in the model, it was not associated with CPA (P=0.50). Furthermore, there was a significant correlation of CPA with plasma H(e) (r=0.23, P<0.0001). However, the mean CPA did not differ between subjects according to genotype.
Conclusions—Thus, plasma H(e), but not MTHFR genotype, is significantly associated with carotid atherosclerosis, suggesting that the biochemical test may be sufficient to identify patients who may be at increased risk of atherosclerosis through this mechanism.
Key Words: carotid arteries • genetics • polygenic disease • risk factors
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