Beeks Esther, van der Klauw Melanie M, Kroon Abraham A, Spiering Wilko, Fuss-Lejeune Monique J M J, de Leeuw Peter W
Department of Medicine, Cardiovascular Research Institute Maastricht (CARIM), University Hospital Maastricht, Maastricht, The Netherlands.
Hypertension. 2004 Oct;44(4):419-23. doi: 10.1161/01.HYP.0000141410.72537.fd. Epub 2004 Aug 23.
Previous studies have shown an association between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. Not much is known about the effects of the variants of this polymorphism on renal hemodynamics and function. Therefore, we performed the present study to investigate the effect of the 460Trp allele of the alpha-adducin gene on renal hemodynamics in one hundred and seventeen essential hypertensive patients who were put on a low and high sodium diet (randomized order). On the last day of each one-week dietary period, blood pressure, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and neurohormones were measured. Effective renal blood flow (ERBF), renal vascular resistance, and filtration fraction were calculated. ERPF, ERBF, and GFR were lower in patients homozygous for the 460Trp allele compared with patients with the Gly460Gly genotype on low sodium diet but no differences were found at the higher sodium intake. On the other hand, levels of atrial natriuretic peptide were significantly higher in patients with the Trp460Trp genotype as compared with patients with the Gly460Gly genotype on both diets. In multivariate analysis, Trp460Trp genotype, age, and mean arterial pressure were predictors of ERPF, whereas Trp460Trp genotype and age were predictors of GFR during the phase of low sodium diet. The present study shows that the Trp460Trp genotype is significantly associated with reduced renal plasma flow and glomerular filtration rate as compared with the wild-type variant.
先前的研究表明,α-内收蛋白Gly460Trp基因多态性与盐敏感性高血压之间存在关联。关于这种多态性变体对肾血流动力学和功能的影响,目前所知甚少。因此,我们进行了本研究,以调查α-内收蛋白基因的460Trp等位基因对117例原发性高血压患者肾血流动力学的影响,这些患者采用低钠和高钠饮食(随机顺序)。在每个为期一周的饮食期的最后一天,测量血压、有效肾血浆流量(ERPF)、肾小球滤过率(GFR)和神经激素。计算有效肾血流量(ERBF)、肾血管阻力和滤过分数。在低钠饮食时,460Trp等位基因纯合子患者的ERPF、ERBF和GFR低于Gly460Gly基因型患者,但在高钠摄入时未发现差异。另一方面,在两种饮食中,Trp460Trp基因型患者的心房利钠肽水平均显著高于Gly460Gly基因型患者。在多变量分析中,Trp46Trp基因型、年龄和平均动脉压是低钠饮食阶段ERPF的预测因素,而Trp460Trp基因型和年龄是GFR的预测因素。本研究表明,与野生型变体相比Trp460Trp基因型与肾血浆流量和肾小球滤过率降低显著相关。