Association of PLA2G7 polymorphisms with carotid atherosclerosis in hypertensive Japanese

Although the plasma platelet-activating factor-acetylhydrolase (pPAF-AH) gene (PLA2G7) polymorphisms are reportedly associated with atherosclerotic diseases, their effects in hypertensive patients have not been well examined. Thus, we genotyped V279F, a loss-of-function mutation commonly seen in the Japanese, and I198T and A379V commonly seen in Caucasians, and investigated the (1) ethnic differences in the frequencies and (2) association of these variants with prevalence of carotid plaque in 733 treated hypertensive Japanese patients. The distribution of V279F (V allele 75.1% and F allele 24.9%) in hypertensive patients was similar to that previously reported in the healthy Japanese; however, allele frequencies of I198T (I allele 71.7% and T allele 28.3%) and A379V (A allele 84.7% and V allele 15.3%) were markedly different from those reported in Caucasians. In addition, V279F and I198T showed a strong linkage disequilibrium (D'=1.0, r(2)=0.89). The phenotypes showed no difference among genotypes for each polymorphism except for the blood pressure level in I198T in women. Carotid plaque was significantly more prevalent in subjects with 279F and 198T than in those with the wild type among men but not women, whereas A379V did not affect it. In multivariate logistic regression analyses, 279F and 198T were detected as an independent risk factor even after adjustments for other atherosclerotic risk factors in men. Taken together, our data suggest an ethnic difference and the possible involvement of genetic polymorphisms of PLA2G7 in the prevalence of carotid atherosclerosis in the hypertensive Japanese, especially in men.