Lieb Wolfgang, Graf Jochen, Götz Anika, König Inke R, Mayer Björn, Fischer Marcus, Stritzke Jan, Hengstenberg Christian, Holmer Stephan R, Döring Angela, Löwel Hannelore, Schunkert Heribert, Erdmann Jeanette
Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germany.
J Mol Med (Berl). 2006 Jan;84(1):88-96. doi: 10.1007/s00109-005-0718-5. Epub 2005 Nov 11.
Angiotensin-converting enzyme (ACE) activity is considered to be of major importance for the conversion of angiotensin (Ang) I to Ang II. Recently, a second ACE, named ACE2, has been identified. Experimental data provide evidence that ACE2 might be involved in modulating cardiac structure and function. In the present explorative study, we assessed whether polymorphisms in the ACE2 gene are related to echocardiographically determined parameters of left ventricular mass, structure or function in the general population. Five intronic single nucleotide polymorphisms (SNPs) were genotyped using the 5'-exonuclease activity (TaqMan) assay in the echocardiographic substudy of the third MONICA Augsburg survey. As ACE2 is located on the X chromosome, women and men were analysed separately. Four SNPs showed high pairwise linkage disequilibrium (rs4646156, rs879922, rs4240157 and rs233575). The minor alleles of these four SNPs were associated with higher left ventricular mass index (LVMI) and higher septal wall thickness (SWT) in men. Likewise, male carriers of a common haplotype (frequency 29.9%) consisting of the minor alleles of these four SNPs displayed higher values for LVMI and SWT than non-carriers (LVMI: TGGC 98.8+/-1.52 vs non-TGGC 94.8+/-0.99 g/m(2), p=0.027; SWT: TGGC 11.5+/-0.14 vs non-TGGC 11.1+/-0.09 mm, p=0.019). Furthermore, this haplotype was associated with an increased odds ratio (OR) for left ventricular hypertrophy (OR 3.10, p=0.006). In women, similar but less pronounced and consistent trends were observed. No association was observed between any of these SNPs and parameters of left ventricular systolic or diastolic function nor with blood pressure levels. This study provides evidence that genetic variants in the ACE2 gene may be associated with left ventricular mass, SWT and left ventricular hypertrophy in hemizygous men.
血管紧张素转换酶（ACE）活性被认为在血管紧张素（Ang）I 转化为 Ang II 的过程中起主要作用。最近，已鉴定出第二种 ACE，即 ACE2。实验数据表明 ACE2 可能参与调节心脏结构和功能。在本探索性研究中，我们评估了 ACE2 基因多态性是否与一般人群中经超声心动图测定的左心室质量、结构或功能参数相关。在第三次奥格斯堡 MONICA 调查的超声心动图子研究中，使用 5' 核酸外切酶活性（TaqMan）分析法对五个内含子单核苷酸多态性（SNP）进行了基因分型。由于 ACE2 位于 X 染色体上，因此对女性和男性分别进行了分析。四个 SNP 显示出高度的成对连锁不平衡（rs4646156、rs879922、rs4240157 和 rs233575）。这四个 SNP 的次要等位基因与男性较高的左心室质量指数（LVMI）和较高的室间隔厚度（SWT）相关。同样，由这四个 SNP 的次要等位基因组成的常见单倍型（频率为 29.9%）的男性携带者的 LVMI 和 SWT 值高于非携带者（LVMI：TGGC 98.8±1.52 与非 TGGC 94.8±0.99 g/m²，p = 0.027；SWT：TGGC 11.5±0.
