[Plasma platelet-activating factor acetylhydrolase (PAF-AH) deficiency as a risk factor for stroke].

Platelet-activating factor (PAF) is a phospholipid mediator with a wide range of potent biological activities. The molecular structure of PAF is identified as 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine and it is degraded by the enzyme PAF acetylhydrolase (PAF-AH), which removes the sn-2 acetyl moiety of the molecule. Plasma PAF-AH activity is elevated in various disorders, including stroke, and this is considered an adaptation to the enhanced inflammatory or thrombotic processes in such disorders. Deficiency of plasma PAF-AH occurs due to a missense mutation (G994-->C) in exon 9 of the PAF-AH gene, which results in a Val-->Phe substitution at position 279 of the mature enzyme protein. This mutation is found in about 4% of the general Japanese population. However, it is not specifically related to any particular disease. The prevalence of plasma PAF-AH deficiency and the frequency of mutant alleles are significantly higher in patients suffering from stroke as compared to healthy controls. The prevalence of the mutation was similar in the groups of patients with atherothrombotic infarction and intracerebral hemorrhage. There was no difference in the prevalence of the mutation in the patients with essential hypertension as compared to that in healthy in controls. Therefore plasma PAF-AH deficiency may be considered as a genetic risk factor for stroke, and recognition of this mutation in individuals may be useful for early initiation of preventive measures against stroke.