Preliminary studies on human aldosterone synthase (CYP11B2) gene polymorphism, matrix metalloprotease-9, apoptosis, and carotid atherosclerosis plaque size by proton magnetic resonance imaging

摘要

Hypothesis. Aldosterone has direct or indirect effects on atherosclerosis, and polymorphisms occur in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalysing aldosterone biosynthesis. Genetic variations in aldosterone synthesis may influence progression of carotid atherosclerosis. Materials and methods. Ten subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promotor) and the other in the second intron. In vivo plaque size was estimated by H-1 magnetic resonance imaging using gradient echo pulse sequence. Media-intima thickness and ex vivo plaque in endarterectomy samples were measured by histology. Matrix metalloprotease (MMP)-9 was stained in endarterectomy histology sections and apoptosis index was counted in these sections. Results. The CYP11B2 promoter genotype patterns were associated significantly with the plaque size in carotid artery (r2=0.9987; p=0.001), MMP-9 levels (r 2=0.9878; p=0.0001) and apoptotic indices (r2=0.9495; p=0.005) by multiple regression analysis. The media-intima thickness was not significantly correlated with genotype patterns. Conclusion. Genetic variations in aldosterone synthase (CYP11B2) gene are associated with the progression of atherosclerotic plaque size, MMP-9 and apoptosis in the carotid artery.