Identification of the G994--> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men.

Platelet-activating factor (PAF) acetylhydrolase may play important roles in the pathophysiology of thrombosis and atherosclerosis related to its catalytic action in the degradation of PAF and oxidized phospholipids. A missense mutation (G--> T transversion at nucleotide 994) in the plasma PAF acetylhydrolase gene results in a Val--> Phe substitution at amino acid 279 of the mature protein and a consequent loss of catalytic activity. However, the role of a deficiency or low activity of this enzyme caused by the missense mutation in the etiology of coronary artery disease (CAD) has not been determined. The relation between this mutation and the incidence of CAD in the Japanese population is investigated herein. The genotype of plasma PAF acetylhydrolase (MM, normal; Mm, heterozygote; and mm, deficient homozygote) was determined with a polymerase chain reaction (PCR) assay for 454 patients with myocardial infarction (MI) and 602 control subjects. The frequency of the m allele was significantly higher in male patients with MI (odds ratio, 1.8) than in controls, an association that was more marked in a low-risk subgroup (odds ratio, 2.3). In contrast, the m allele was not associated with MI in women. These results indicate that the G994--> T missense mutation in exon 9 of the plasma PAF acetylhydrolase gene is an independent risk factor for CAD in Japanese men, especially low-risk individuals, but not in women.