A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke.
OBJECTIVE
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 (Val279-->Phe). We have studied a possible association of this mutation with the risk of stroke.


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) (chi 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.
Hiramoto
M
M
Department of Pathological Physiology, Hirosaki University School of Medicine, Japan.
Yoshida
H
H
Imaizumi
T
T
Yoshimizu
N
N
Satoh
K
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000368:Aged; D000595:Amino Acid Sequence; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D002542:Intracranial Embolism and Thrombosis / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010741:Phospholipases A / Q000097:blood* / Q000172:deficiency / Q000235:genetics*; D015995:Prevalence; D012016:Reference Values; D012307:Risk Factors
D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase