A mutation in plasma platelet-activating factor acetylhydrolase gene (G(994)-> T) is a genetic risk factor for stroke

Platelet-activating factor (PAF) is a potent bioactive phospholipid with a wide variety of functions. In plasma, it is inactivated by a specific enzym e PAF acetylhydrolase. Deficiency of this enzyme is due to a point mutation in the gene (G(994)-->T); and the appearance of the mutation is more commo n in the Japanese than in Caucasians. When analysing about 1,000 blood samp les from the general Japanese population, we found the homozygous deficienc y in 4% of cases who lacked completely enzyme activity in plasma. This fact may imply that the mutation is associated with the risk of certain multifa ctorial diseases relatively common among the Japanese. Based on this hypoth esis, we studied the relation of this mutation with risk for stroke and fou nd a higher incidence of the mutation of plasma PAF acetylhydrolase gene in patients with cerebral thrombosis as compared to control subjects. The fre quency of the mutant allele was 1.7 times more common in patients than in c ontrols. This suggests that plasma PAF acetylhydrolase deficiency may be a genetic risk factor for stroke.