Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function.
Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function.
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DOI：
10.1161/01.cir.97.6.569
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发表时间：
1998-02
期刊：
影响因子：
37.8
通讯作者：
M. Kupari;A. Hautanen;L. Lankinen;P. Koskinen;J. Virolainen;H. Nikkila;P. White
中科院分区：
文献类型：
--
作者：
M. Kupari;A. Hautanen;L. Lankinen;P. Koskinen;J. Virolainen;H. Nikkila;P. White
背景技术醛固酮对心脏有直接和间接的影响，因此醛固酮合成的遗传变异可能影响心脏的结构和功能。这种变异可能与编码醛固酮合酶（CYP11B2）的基因多态性有关，该酶催化醛固酮生物合成的最后步骤。方法和结果 通过 M 型和多普勒超声心动图对 84 名年龄在 36 至 37 岁之间的芬兰人口样本（44 名女性）进行研究，以评估左心室大小、质量和功能。通过使用聚合酶链式反应对 CYP11B2 中的两个二等位基因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。在多元回归分析中，CYP11B2 启动子基因型预测左心室舒张末期直径 (beta=.40，P<.0001)、收缩末期直径 (beta=.33，P=.0009) 和质量 (beta=.17，P=.023) 的统计显着变化。这些影响独立于潜在的混杂因素，包括性别、体型、血压、体力活动、吸烟和乙醇消耗。基因型组在左心室舒张功能、心率调整心房充盈分数方面也存在差异 (P=.018)。已知饮食盐增加可预测左心室质量增加，但这种效应仅与某些 CYP11B2 基因型相关 (P<.001)。结论 醛固酮合酶 (CYP11B2) 基因或其附近的遗传变异强烈影响无临床心脏病的年轻人的左心室大小和质量。这些多态性也可能影响左心室对膳食盐增加的反应。
BACKGROUND Aldosterone has direct and indirect effects on the heart, and genetic variations in aldosterone synthesis could therefore influence cardiac structure and function. Such variations might be associated with polymorphisms in the gene encoding aldosterone synthase (CYP11B2), the enzyme catalyzing the last steps of aldosterone biosynthesis. METHODS AND RESULTS A Finnish population sample of 84 persons (44 women) aged 36 to 37 years was studied by M-mode and Doppler echocardiography to assess left ventricular size, mass, and function. Subjects were genotyped through the use of the polymerase chain reaction for two diallelic polymorphisms in CYP11B2: one in the transcriptional regulatory region (promoter) and the other in the second intron. In multiple regression analyses, the CYP11B2 promoter genotype predicted statistically significant variations in left ventricular end-diastolic diameter (beta=.40, P<.0001), end-systolic diameter (beta=.33, P=.0009), and mass (beta=.17, P=.023). These effects were independent of potentially confounding factors, including sex, body size, blood pressure, physical activity, smoking, and ethanol consumption. Genotype groups also differed in a measure of left ventricular diastolic function, the heart rate-adjusted atrial filling fraction (P=.018). Increased dietary salt, which is known to predict increased left ventricular mass, had this effect only in association with certain CYP11B2 genotypes (P<.001). CONCLUSIONS Genetic variations in or near the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in young adults free of clinical heart disease. These polymorphisms may also influence the response of the left ventricle to increases in dietary salt.