Naturally Occurring Missense Mutation in Plasma PAF-AH Among the Japanese Population.

A single nucleotide polymorphism in the plasma PAF-AH enzyme, i.e., G994T, which causes the substitution of Val at amino acid 279 with Phe (V279F), has been found in the Japanese population. This enzyme preferentially degrades oxidatively modulated or truncated phospholipids; therefore, it has been suggested that this enzyme may prevent the accumulation of proinflammatory and proatherogenic oxidized phospholipids. This hypothesis is supported by the higher prevalence of the V279F mutation in patients with asthmatic and atherosclerotic diseases, as compared with healthy controls. This mutation is rare in the Caucasian population. The plasma PAF-AH mass and enzyme activity are distributed over a wide range in the plasma and they are positively correlated with low-density lipoprotein (LDL) cholesterol. However, several clinical studies in the Caucasian population have suggested that this enzyme has the opposite role. This enzyme plays an active role in the development and progression of atherosclerosis via proinflammatory and proatherogenic lysophosphatidylcholine and oxidized fatty acids produced through the oxidation of LDL by this enzyme. Thus, plasma PAF-AH is a unique enzyme with dual roles in human inflammatory diseases. In this chapter, on the basis of recent findings we describe the association between a naturally occurring missense mutation in plasma PAF-AH and human diseases especially including atherosclerosis and asthma.