NOS3 Polymorphisms and Chronic Kidney Disease

ABSTRACT Chronic kidney disease (CKD) is a multifactorial pathophysiologic irreversible process that often leads to a terminal state in which the patient requires renal replacement therapy. Most cases of CKD are due to chronic-degenerative diseases and endothelial dysfunction is one of the factors that contribute to its pathophysiology. One of the most important mechanisms for proper functioning of the endothelium is the regulation of the synthesis of nitric oxide. This compound is synthesized by the enzyme nitric oxide synthase, which has 3 isoforms. Polymorphisms in the NOS3 gene have been implicated as factors that alter the homeostasis of this mechanism. The Glu298Asp polymorphisms 4 b/a and -786T>C of the NOS3 gene have been associated with a more rapid deterioration of kidney function in patients with CKD. These polymorphisms have been evaluated in patients with CKD of determined and undetermined etiology and related to a more rapid deterioration of kidney function.

摘要 慢性肾脏病（CKD）是一种多因素参与的病理生理不可逆进程，常进展至需接受肾脏替代治疗的终末期。多数慢性肾脏病病例由慢性退行性疾病引发，而内皮功能障碍是参与其病理生理过程的因素之一。维持内皮正常功能的关键机制之一是对一氧化氮合成的调控。该化合物由一氧化氮合酶合成，而一氧化氮合酶存在3种同工型。NOS3基因多态性被认为是改变该机制稳态的相关因素。已有研究证实，NOS3基因的Glu298Asp、4b/a及-786T>C多态性与慢性肾脏病患者肾功能更快恶化相关。上述多态性已在明确病因及不明病因的慢性肾脏病患者中开展评估，并被证实与肾功能更快恶化存在关联。