Association of a G994 -->T missense mutation in the plasma platelet-activating factor acetylhydrolase gene with risk of abdominal aortic aneurysm in Japanese.

Objective: To investigate a possible association with plasma platelet activating factor acetylhydrolase (PAF-AH) gene mutation with the risk of abdominal aortic aneurysm (AAA).
Summary Background Data: Plasma platelet activating factor acetylhydrolase is known to catalyze platelet activating factor (PAF), thereby inactivating its inflammatory function. Deficiency of this enzyme is caused by a missense mutation (G994 -->T) in exon 9 of the plasma PAF-AH gene.
Methods: We did a case-control study including 131 patients (median age 73.4 [range 50-84] years) and 106 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.
Results: The frequency of the mutant allele (T allele) in the plasma PAF-AH gene in AAA patients was significantly higher than in control subjects. The association of the missense mutation with AAA was statistically significant and independent of other risk factors. Among AAA patients with normal genomic type, plasma PAF-AH activity was strongly correlated to the plasma concentration of low density lipoprotein cholesterol (LDL-C), while the correlation was not observed among AAA patients with heterozygotes genotype. Patients having AAA with both T allele and hyperlipidemia were more likely to have other atherosclerotic diseases such as ischemic heart disease, stroke and peripheral arterial occlusive diseases than patients with the normal genomic type and normal lipid level.
Conclusions: The genetic mutation of plasma PAF-AH gene appear to be an independent risk factor for AAA. Our findings need to be confirmed in a larger, prospective study including patients from different populations.