Background: Although several genes or genetic loci that are responsible for or confer susceptibility to familial dilated cardiomyopathy (DCM) have been identified, genetic defects that underlie nonfamilial DCM remain to be characterized. Mice lacking manganese superoxide dismutase exhibit DCM, suggesting that impairment of the defense mechanisms against oxidative stress is an important susceptibility factor for DCM. Plasma platelet-activating factor (PAF) acetylhydrolase also acts as a key defense against oxidative stress by hydrolyzing PAF and oxidized phospholipids. Thus, abnormalities in the activity of this enzyme may result in predisposition to myocardial damage.
Methods and results: The possible association of a G994 (M allele)-->T (m allele) missense mutation in the plasma PAF acetylhydrolase gene with genetic susceptibility to nonfamilial DCM has now been investigated in 122 Japanese individuals with this condition and 226 healthy control subjects. PAF acetylhydrolase activity in plasma was significantly associated with plasma PAF acetylhydrolase genotype in both DCM patients and healthy control subjects. The frequency of the mutant m allele was significantly higher in DCM patients than in control subjects. Left ventricular mass (LVM) and the LVM index in DCM patients with Mm or mm genotypes were significantly greater than those in patients with the MM genotype.
Conclusions: The G994-->T mutation in the plasma PAF acetylhydrolase gene is associated with nonfamilial DCM in Japanese subjects. Although the mutation is unlikely to be a causative factor, it may contribute to genetic susceptibility to or progression of nonfamilial DCM.