Division of Nephrology, Department of Medicine, University of Rochester Medical Center, NY.
Hypertension. 2021 Sep;78(4):936-945. doi: 10.1161/HYPERTENSIONAHA.121.16510. Epub 2021 Aug 30.
In the United States, the prevalence of chronic kidney disease in adults is ≈14%. The mainstay of therapy for chronic kidney disease is angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but many patients with chronic kidney disease still progress to end-stage kidney disease. Increased oxidative stress is a major molecular underpinning of chronic kidney disease progression. In humans, a common deletion variant of the glutathione-S-transferase μ-1 () gene, the null allele ()), results in decreased GSTM1 enzymatic activity and is associated with higher levels of oxidative stress. GSTM1 belongs to the superfamily of GSTs that are phase II antioxidant enzymes and are regulated by Nrf2 (nuclear factor erythroid 2-related factor 2). Cruciferous vegetables in general, and broccoli in particular, are rich in glucoraphanin, a precursor of sulforaphane that has been shown to have protective effects against oxidative damage through the activation of Nrf2. This review will highlight recent human and animal studies implicating the role of GSTM1 deficiency in hypertension and kidney disease, and its impact on the effects of cruciferous vegetables on kidney injury and disease progression, illustrating the significance of gene and environment interaction and a potential for targeted precision medicine in the treatment of kidney disease.
在美国,成年人慢性肾脏病的患病率约为 14%。慢性肾脏病的主要治疗方法是血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂,但许多慢性肾脏病患者仍会进展为终末期肾病。氧化应激增加是慢性肾脏病进展的主要分子基础。在人类中,谷胱甘肽 S-转移酶 μ-1(GSTM1)基因的常见缺失变异(null 等位基因())导致 GSTM1 酶活性降低,并与更高水平的氧化应激相关。GSTM1 属于 GST 超家族,是 II 相抗氧化酶,受 Nrf2(红细胞生成素 2 相关因子 2)调节。十字花科蔬菜一般,特别是西兰花,富含萝卜硫素的前体物——葡萄糖苷芸苔素,已证明其通过激活 Nrf2 对氧化损伤具有保护作用。本综述将重点介绍最近的人类和动物研究,这些研究表明 GSTM1 缺乏与高血压和肾脏病有关,及其对十字花科蔬菜对肾脏损伤和疾病进展影响,说明了基因与环境相互作用的意义和针对肾脏病治疗的靶向精准医学的潜力。