Background: Plasma PAF-acetylhydrolase (PAF-AH) gene polymorphisms (G994 --> T in exon 9) and the resulting deficiency of enzyme activity were identified in the Japanese population. The objective of this study was to assess the joint effect of the polymorphism and hypercholesterolemia on risk of atherosclerosis.
Methods and results: We performed a case-control study including 150 patients who underwent operation for peripheral arterial occlusive disease (PAOD) and 158 controls matched for age and sex. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in both groups. The patients with multiple atherosclerotic diseases showed higher levels of PAF-AH activities than the patients with only peripheral artery occlusive disease among normal genotypes. PAOD patients were assessed either with or without polymorphism or hypercholesterolemia in regard to accompanying coronary artery disease or stroke. The prevalence of the polymorphism was significantly more frequent in the patients with PAOD. The plasma PAF-AH activity was correlated with total cholesterol and LDL level, and inversely related with HDL in normal genotype (GG) PAOD patients. However, neither the correlation nor the inverse relation was found in patients with the polymorphism. Patients with both hypercholesterolemia and the polymorphisms revealed a relative risk for other atherosclerotic disease of 11.5 (6.0-40.3) compared with normal genotype and normal lipid level.
Conclusion: The plasma PAF-AH gene polymorphism and hypercholesterolemia may interact and increase the risk of atherosclerosis.