肾素-血管紧张素-醛固酮基因型影响单心室婴儿的心室重构。
Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle.
机构信息
Division of Pediatric Cardiology Hospital for Sick Children, Toronto, Ontario, Canada.
出版信息
Circulation. 2011 May 31;123(21):2353-62. doi: 10.1161/CIRCULATIONAHA.110.004341. Epub 2011 May 16.
BACKGROUND
We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle.
METHODS AND RESULTS
Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those with <2 homozygous risk genotypes (low risk) at 2 time points: before the superior cavopulmonary connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (P<0.05), but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline, and height remained lower in the high-risk group at 14 months, especially in those receiving enalapril (P<0.05).
CONCLUSIONS
Renin-angiotensin-aldosterone system-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact.
CLINICAL TRIAL REGISTRATION
http://www.clinicaltrials.gov. Unique identifier: NCT00113087.
背景
我们研究了肾素-血管紧张素-醛固酮系统（RAAS）基因多态性对单心室婴儿心室重构、生长、肾功能以及依那普利反应的影响。
方法和结果
参加依那普利随机试验的单心室婴儿接受了 5 个基因（血管紧张素原、血管紧张素转换酶、血管紧张素 II 型 1 型受体、醛固酮合酶和糜酶）多态性的基因分型。将与肾素-血管紧张素-醛固酮系统上调相关的等位基因归类为风险等位基因。在两个时间点（上腔静脉肺动脉吻合术（SCPC）前和 14 月龄），比较了至少 2 个纯合风险基因型（高风险）和<2 个纯合风险基因型（低风险）的患者之间的心室质量、容量、体生长、估计肾小球滤过率（eGFR）和依那普利反应。在 230 例试验对象中，有 154 例进行了基因分型：38 例为高风险，116 例为低风险。两组患者在 SCPC 前心室质量和容量均升高。低风险组在 SCPC 后心室质量和容量下降，eGFR 增加（P<0.05），而高风险组则无此变化。这些反应与依那普利治疗无关。在基线时，体重和身高 z 评分较低，高风险组在 14 月龄时身高仍然较低，尤其是接受依那普利治疗的患者（P<0.05）。
结论
RAAS 上调基因型与 SCPC 手术后反向重构失败、肾功能改善减少以及体生长受损相关，后者在接受依那普利治疗的患者中更为明显。RAAS 基因型可能确定了一组不能从容量负荷减轻手术中充分获益的单心室患者的高危亚组。需要进行随访以评估长期影响。
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