© 1999 American Heart Association, Inc.
Original Contributions |
Genetic Analysis of the Thermolabile Variant of 5,10-Methylenetetrahydrofolate Reductase as a Risk Factor for Ischemic Stroke
From Trinity College, Dublin, Ireland (D.L.H., D.C.S., A.S.W.); Mercer's Institute for Research on Ageing, St James's Hospital, Dublin, Ireland (R.M.D., M.D., D.C.); and the Department of Cardiology, Adelaide Hospital, Dublin, Ireland (R.M., R.B., I.M.G.). Dr Harmon is now in the Pathology Department, Biotechnology Centre, University College Dublin, Belfield, Ireland. Dr Whitehead is now in the Department of Pharmacology and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pa.
Correspondence to Alexander S. Whitehead, DPhil, Department of Pharmacology and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084. E-mail aswhitehead{at}pharm.med.upenn.edu
Abstract—Mild
hyperhomocysteinemia is a risk factor for atherosclerotic vascular
disease. Homozygosity for the C677T mutation in the gene for
5,10-methylenetetrahydrofolate
reductase (MTHFR) is frequently associated with hyperhomocysteinemia,
particularly in individuals with low levels of serum folate, and has
been directly associated with cardiovascular disease in
certain populations. The purpose of this study was to establish whether
the C677T mutation, which causes thermolabile MTHFR, is a risk factor
for ischemic stroke in the Irish population. The homozygous
C677T genotype has previously been associated with
coronary heart disease in Ireland. We collected blood
from 174 individuals (minimum age 60 years) who had suffered an
ischemic stroke that was confirmed by computed tomography brain
scan. Control subjects (n=183) aged 
60 years, who had never suffered
a stroke or transient ischemic attack, were recruited from
hospitals and active retirement groups in the same geographical area.
MTHFR genotypes were determined and other known risk factors
for stroke were documented. In the control group, the frequency of
subjects with the homozygous C677T genotype was 10.4%. In
patients who had suffered ischemic stroke, the frequency was
15.5%. This difference was not statistically significant. The odds
ratio of stroke for C677T homozygotes, with other genotypes as
a reference group, was 1.59, 95% CI=0.85, 2.97. The data indicate
that the homozygous C677T MTHFR genotype is at most a moderate
risk factor for ischemic stroke.
Key Words: homocysteine • genetics • MTHFR • ischemic stroke
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