Pedrinelli Roberto, Dell'Omo Giulia, Penno Giuseppe, Di Bello Vitantonio, Pucci Laura, Fotino Carmen, Lucchesi Daniela, Del Prato Stefano, Dal Fiume Chiara, Barlassina Cristina, Cusi Daniele
Dipartimento Cardio Toracico, Università di Pisa, Pisa, Italy.
J Hypertens. 2006 May;24(5):931-7. doi: 10.1097/01.hjh.0000222764.92229.6d.
A single-nucleotide polymorphism (Gly460Trp) within the alpha-adducin gene (ADD1) may influence several renal phenotypes, including salt sensitivity, susceptibility to renal failure, the renal haemodynamics and confer a worse cardiovascular risks profile. However, its relationship with microalbuminuria, a marker of early renal and cardiovascular damage and an independent predictor of morbid events in hypertension, is unknown. For this reason, we related the ADD1 genetic polymorphism to urine albumin levels and other clinical variables in essential hypertensive men. The angiotensin-converting enzyme (ACE) insertion/deletion (ID) polymorphism was also evaluated because of its interactive potential with the ADD1 genotype.
Albuminuria (three overnight collections), echocardiographic left ventricular mass index, blood pressure, body mass index, renal function, glucose and lipids were measured in 238 genetically unrelated, never treated, uncomplicated Caucasian essential hypertensive men. Polymerase chain reaction or a 5' nuclease assay were used to characterize the ACE ID and ADD1 Gly460Trp variants, respectively.
Microalbuminuria (albuminuria >or= 15 microg/min) was more frequent in patients with the ACE DD variant, but only in those with a ADD1 Gly460Gly background. In contrast, urine albumin did not differ by ACE ID genotype in the presence of mutated ADD1 Trp alleles. ADD1 polymorphisms per se were not associated with albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously distributed among different genetic backgrounds.
ACE DD and ADD1 Gly460Gly polymorphisms may jointly influence albuminuria in hypertensive men, 460Gly homozygosis facilitating or, possibly, the 460Trp allele mitigating the noxious renal impact of the ACE DD genotype. The data highlight further the complex pathophysiological implications of microalbuminuria in hypertension.
α-内收蛋白基因（ADD1）内的单核苷酸多态性（Gly460Trp）可能影响多种肾脏表型，包括盐敏感性、肾衰竭易感性、肾脏血流动力学，并导致更差的心血管风险状况。然而，其与微量白蛋白尿（早期肾脏和心血管损伤的标志物以及高血压患者发病事件的独立预测因子）之间的关系尚不清楚。因此，我们在原发性高血压男性中将ADD1基因多态性与尿白蛋白水平及其他临床变量相关联。由于血管紧张素转换酶（ACE）插入/缺失（ID）多态性与ADD1基因型存在潜在相互作用，因此也对其进行了评估。
对238名无亲缘关系、未经治疗、无并发症的白种人原发性高血压男性测量了蛋白尿（三个夜间收集样本）、超声心动图左心室质量指数、血压、体重指数、肾功能、血糖和血脂。分别使用聚合酶链反应或5'核酸酶分析来鉴定ACE ID和ADD1 Gly460Trp变体。
ACE DD变体患者中微量白蛋白尿（蛋白尿≥15微克/分钟）更常见，但仅在具有ADD1 Gly460Gly背景的患者中如此。相比之下，在存在突变的ADD1 Trp等位基因时，尿白蛋白在不同ACE ID基因型之间无差异。ADD1多态性本身与蛋白尿无关。心血管、肾脏、代谢参数在不同遗传背景之间均匀分布。
ACE DD和ADD1 Gly460Gly多态性可能共同影响高血压男性的白蛋白尿，460Gly纯合子起促进作用，或者460Trp等位基因可能减轻ACE DD基因型对肾脏的有害影响。这些数据进一步凸显了微量白蛋白尿在高血压中复杂的病理生理意义。
