Sciarrone Maria Teresa, Stella Paola, Barlassina Cristina, Manunta Paolo, Lanzani Chiara, Bianchi Giuseppe, Cusi Daniele
Department of Nephrology and Graduate School of Nephrology Universita' Vita e Salute, Milan, Italy.
Hypertension. 2003 Mar;41(3):398-403. doi: 10.1161/01.HYP.0000057010.27011.2C. Epub 2003 Feb 24.
Renin-angiotensin system reactivity and the constitutive capacity of the renal tubule to reabsorb sodium play a role in the individual response to diuretic therapy; therefore we evaluated the blood pressure (BP) response to hydrochlorothiazide in 87 never-treated individuals with mild essential hypertension, according to ACE gene I/D and alpha-adducin Gly460Trp polymorphism. These genotypes where chosen because previous data showed their interaction in determining the BP response to salt probably was the result of their involvement in the activation of the renin-angiotensin system (ACE) and in the constitutive capacity of the kidney to reabsorb sodium (alpha-adducin) (treatment for 2 months). BP was measured after 3 run-in visits and after the first and second months of treatment by means of a standardized procedure. Data were analyzed by ANOVA, t test, and multivariate ANOVA for repeated measures (covarying for gender, age, and body mass index). Although basal mean BP (MBP) was similar in the different ACE and alpha-adducin genotypes, patients carrying at least one I allele of ACE and one 460Trp allele of alpha-adducin had the largest MBP decrease with treatment (12.7+/-1.9 mm Hg), the effect of the combination of genotypes being additive but not epistatic. These patients had an odds ratio of 15.75 of being a responder to hydrochlorothiazide compared with patients with Gly460Gly+DD, with the least MBP decrease (3.4+/-1.7 mm Hg). Alpha-adducin and ACE I/D polymorphism may be useful to predict the interindividual degree of response to hydrochlorothiazide; the analysis of the combination of the 2 genotypes increases the accuracy of the prediction of response to the drug.
肾素-血管紧张素系统反应性以及肾小管重吸收钠的固有能力在个体对利尿剂治疗的反应中发挥作用；因此，我们根据ACE基因I/D和α-内收蛋白Gly460Trp多态性，评估了87名未经治疗的轻度原发性高血压患者对氢氯噻嗪的血压（BP）反应。选择这些基因型是因为先前的数据表明，它们在决定对盐的BP反应中的相互作用可能是由于它们参与肾素-血管紧张素系统（ACE）的激活以及肾脏重吸收钠的固有能力（α-内收蛋白）（治疗2个月）。在3次导入访视后以及治疗的第1个月和第2个月后，通过标准化程序测量BP。数据通过方差分析、t检验和重复测量的多变量方差分析（对性别、年龄和体重指数进行协变量分析）进行分析。尽管不同ACE和α-内收蛋白基因型的基础平均血压（MBP）相似，但携带至少一个ACE的I等位基因和一个α-内收蛋白的460Trp等位基因的患者在治疗后MBP下降最大（12.7±1.9 mmHg），基因型组合的效应是相加的而非上位性的。与Gly460Gly + DD患者相比，这些患者对氢氯噻嗪有反应的优势比为15.75，其MBP下降最少（3.4±1.7 mmHg）。α-内收蛋白和ACE I/D多态性可能有助于预测个体对氢氯噻嗪的反应程度；对这两种基因型组合的分析提高了对药物反应预测的准确性。
