Cardiology Division, Columbia University, New York, NY 10032, USA.
J Renin Angiotensin Aldosterone Syst. 2010 Sep;11(3):198-204. doi: 10.1177/1470320309358109. Epub 2010 Feb 1.
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.
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.
The CYP11B2 promoter genotype patterns were associated significantly with the plaque size in carotid artery (r(2)=0.9987; p=0.001), MMP-9 levels (r( 2)=0.9878; p=0.0001) and apoptotic indices (r(2)=0.9495; p=0.005) by multiple regression analysis. The media-intima thickness was not significantly correlated with genotype patterns.
Genetic variations in aldosterone synthase (CYP11B2) gene are associated with the progression of atherosclerotic plaque size, MMP-9 and apoptosis in the carotid artery.
醛固酮对动脉粥样硬化有直接或间接的影响，醛固酮合酶（CYP11B2）基因发生多态性，该酶催化醛固酮的生物合成。醛固酮合成的遗传变异可能会影响颈动脉粥样硬化的进展。
通过聚合酶链反应对 CYP11B2 的两个二态多态性进行基因分型：一个位于转录调控区（启动子），另一个位于第二内含子。通过 H-1 磁共振成像使用梯度回波脉冲序列来估计体内斑块大小。通过组织学测量内膜中层厚度和内膜切除术样本中的外生斑块。在内膜切除术组织学切片中染色基质金属蛋白酶（MMP）-9，并在这些切片中计算细胞凋亡指数。
CYP11B2 启动子基因型模式与颈动脉斑块大小（r(2)=0.9987；p=0.001）、MMP-9 水平（r( 2)=0.9878；p=0.0001）和细胞凋亡指数（r(2)=0.9495；p=0.005）呈显著相关。多重回归分析显示，内膜中层厚度与基因型模式无显著相关性。
醛固酮合酶（CYP11B2）基因的遗传变异与颈动脉粥样硬化斑块大小、MMP-9 和细胞凋亡的进展有关。
