(Stroke. 1997;28:2417-2420.)
© 1997 American Heart Association, Inc.
Articles |
A Mutation in Plasma Platelet-Activating Factor Acetylhydrolase (Val279
Phe) is a Genetic Risk Factor for Stroke
From the Department of Pathological Physiology (M.H., H.Y., T.I., K.S.), Institute of Neurological Diseases, Hirosaki University School of Medicine, Hirosaki, Japan, and the Department of Neurosurgery (N.Y.), the Yokohama General Hospital, Yokohama, Japan.
Correspondence to Kei Satoh, MD, Department of Pathological Physiology, Institute of Neurological Diseases, Hirosaki University School of Medicine, 5-Zaifucho, Hirosaki 036, Japan. E-mail pathophy{at}cc.hirosaki-u.ac.jp
Background and Purpose Platelet-activating factor (PAF)
is a phospholipid with multiple actions that include thrombosis and
inflammation. It is inactivated by a plasma enzyme, PAF
acetylhydrolase. Deficiency of this enzyme in plasma is caused by a
missense mutation in the gene (Val279Phe). We have
studied a possible association of this mutation with the risk of
stroke.
Subjects and Methods We studied 120 consecutive patients with cerebral thrombosis. The control group consisted of 134 patients matched for age and sex with minor complaints but without stroke. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF acetylhydrolase activity was determined by the method of Stafforini et al.
Results The prevalence of the mutant gene was 43.4% in stroke
patients (39.2% heterozygotes and 4.2% homozygotes), which was
significantly higher than the 25.4% in control subjects (22.4%
heterozygotes and 3.0% homozygotes) (
2=9.22,
P<.01). The prevalence was slightly higher in stroke
patients without hypertension than those with hypertension, but the
difference was not significant. The patients with family histories of
stroke had a slightly higher but not a significant prevalence of the
mutant gene as compared with those without family histories of stroke.
Plasma PAF acetylhydrolase activity was higher in patients than in
control subjects, in normal subjects, or patients with a heterozygous
genotype.
Conclusions These results suggest that plasma PAF acetylhydrolase deficiency may be a risk factor for stroke. This may explain the relatively high prevalence of stroke in Japan, as the mutation is more common among Japanese than Caucasians.
Key Words: cerebral thrombosis • platelet-activating factor • mutation • risk factors
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