A MUTATION IN PLASMA PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE (VAL(279)-]PHE) IS A GENETIC RISK FACTOR FOR STROKE

Background and Purpose Platelet-activating factor (PAF) is a phospholi pid 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 (V al(279) --> Phe). We have studied a possible association of this mutat ion with the risk of stroke. Subjects and Methods We studied 120 conse cutive patients with cerebral thrombosis. The control group consisted of 134 patients matched for age and sex with minor complaints but with out stroke. Genomic DNA was analyzed for the mutant allele by a specif ic polymerase-chain reaction. Plasma PAF acetylhydrolase activity was determined by the method of Stafforini et al. Results The prevalence o f the mutant gene was 43.4% in stroke patients (39.2% heterozygotes an d 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 subjec ts, in normal subjects, or patients with a heterozygous genotype. Conc lusions These results suggest that plasma PAF acetyl hydrolase deficie ncy may be a risk factor for stroke. This may explain the relatively h igh prevalence of stroke in Japan, as the mutation is more common amon g Japanese than Caucasians.