Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake.
Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake.
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DOI：
10.1161/hypertensionaha.115.06415
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Manunta P
中科院分区：
文献类型：
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作者：
Lanzani C;Gatti G;Citterio L;Messaggio E;Delli Carpini S;Simonini M;Casamassima N;Zagato L;Brioni E;Hamlyn JM;Manunta P
内源性哇巴因（EO）的循环水平，肾上腺皮质来源的血管加压激素，增加钠耗竭。此外，羊毛甾醇合酶（LSS），一种参与胆固醇生物合成的酶，具有错义多态性（rs 2254524 V642 L），其影响肾上腺皮质细胞中的EO生物合成。在此，我们研究了轻度原发性高血压患者体内LSS rs 2254524等位基因影响低钠饮食摄入（<100 mEq/d，2周）诱发的BP和EO反应的假设。在低盐饮食期间，（−8.7±1.7 vs −3.0±1.5 p= 0.013），舒张期（−5.1±0.98 vs −1.4± 0.94 mmHg，p<0.05）LSS rs 2254524 A变异体的存在显著影响血压和长期血压-尿钠排泄关系的斜率。（AA：0.71± 0.22，AC 0.09±0.13，CC 0.04±0.11 mEq/mmHg/24 h，p=0.028）。此外，低盐饮食导致约25%的患者血压升高，这与循环EO增加有关。LSS基因多态性影响BP的盐敏感性和低盐饮食引起的循环EO的变化。BP和EO对低盐饮食的反应明显不均匀。大约25%的患者发生了不良反应，即，当盐摄入量减少时，血压和EO增加，可能会增加长期风险。EO对低盐饮食的反应增强进一步支持了某些原发性高血压患者肾上腺皮质功能异常的观点。
Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Further, lanosterol synthase (LSS), an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here we investigated the hypothesis that LSS rs2254524 alleles in vivo impact the BP and EO responses evoked by a low dietary Na intake (<100 mEq/day, 2 weeks) among patients with mild essential hypertension. During the low salt diet, the declines in both systolic (−8.7±1.7 vs −3.0±1.5 p= 0.013), and diastolic (−5.1±0.98 vs −1.4±0,.94 mmHg, p<0.05) BP and the slope of the long-term pressure-natriuresis relationship were affected significantly by the presence of the LSS rs2254524 A variant (AA: 0.71±0,22, AC 0.09±0.13, CC 0.04±0.11 mEq/mmHg/24h, p=0.028). In addition, BP rose in ~25% of the patients in response to the low salt diet and this was associated with increased circulating EO. LSS gene polymorphisms influence both the salt-sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects i.e., increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives.