Ortlepp J R, Vosberg H P, Reith S, Ohme F, Mahon N G, Schröder D, Klues H G, Hanrath P, McKenna W J
Medical Clinic I, Department of Cardiology, University Hospital of Aachen, Aachen, Germany.
Heart. 2002 Mar;87(3):270-5. doi: 10.1136/heart.87.3.270.
Hypertrophic cardiomyopathy (HCM) is an inherited disease of the sarcomere characterised clinically by myocardial hypertrophy and its consequences. Phenotypic expression is heterogeneous even within families with the same aetiological mutation and may be influenced by additional genetic factors.
To determine the influence of genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on ECG and two dimensional echocardiographic left ventricular hypertrophy (LVH) in genetically identical patients with HCM.
Polymorphisms of five RAAS components were determined in 26 gene carriers from a single family with HCM caused by a previously identified myosin binding protein C mutation. Genotypes associated with a higher activation status of the RAAS were labelled "pro-LVH genotypes".
There was a non-biased distribution of pro-LVH genotypes in the gene carriers. Those without pro-LVH genotypes did not manifest cardiac hypertrophy whereas gene carriers with pro-LVH genotypes did (mean (SD) left ventricular muscle mass 190 (48) v 320 (113), p = 0.002; interventricular septal thickness 11.5 (2.0) v 16.4 (6.7), p = 0.01; pathological ECG 0% (0 of 10) v 63% (10 of 16), respectively). Multivariate analysis controlling for age, sex, and hypertension confirmed an independent association between the presence of pro-LVH polymorphisms and left ventricular mass. When each polymorphism was assessed individually, carriers of each pro-LVH genotype had a significantly greater left ventricular mass than those with no pro-LVH mutation; these associations, with the exception of cardiac chymase A AA polymorphism (p = 0.06), remained significant in multivariate analysis.
Genetic polymorphisms of the RAAS influence penetrance and degree of LVH in 26 gene carriers from one family with HCM caused by a myosin binding protein C mutation.
肥厚型心肌病（HCM）是一种肌节遗传性疾病，临床特征为心肌肥厚及其后果。即使在具有相同病因突变的家族中，表型表达也具有异质性，并且可能受其他遗传因素影响。
确定肾素 - 血管紧张素 - 醛固酮系统（RAAS）基因多态性对基因相同的HCM患者心电图及二维超声心动图左心室肥厚（LVH）的影响。
在一个由先前鉴定的肌球蛋白结合蛋白C突变引起的HCM单一家族的26名基因携带者中，测定了5种RAAS成分的多态性。与RAAS较高激活状态相关的基因型被标记为“促LVH基因型”。
促LVH基因型在基因携带者中分布无偏向性。没有促LVH基因型的人未表现出心脏肥厚，而有促LVH基因型的基因携带者则出现了心脏肥厚（平均（标准差）左心室肌肉质量190（48）对320（113），p = 0.002；室间隔厚度11.5（2.0）对16.4（6.7），p = 0.01；病理性心电图分别为0%（10人中0人）对63%（16人中10人））。控制年龄、性别和高血压的多变量分析证实，促LVH多态性的存在与左心室质量之间存在独立关联。当单独评估每种多态性时，每种促LVH基因型的携带者左心室质量均显著大于无促LVH突变者；除心脏糜酶A AA多态性外（p = 0.06），这些关联在多变量分析中仍具有显著性。
RAAS基因多态性影响了一个由肌球蛋白结合蛋白C突变引起的HCM家族中26名基因携带者LVH的外显率和程度。
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