GSTM1 Gene, Diet, and Kidney Disease: Implication for Precision Medicine?: Recent Advances in Hypertension.
GSTM1 Gene, Diet, and Kidney Disease: Implication for Precision Medicine?: Recent Advances in Hypertension.
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DOI：
10.1161/hypertensionaha.121.16510
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发表时间：
2021-09
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影响因子：
--
通讯作者：
Le TH
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作者：
Le TH
在美国，成人慢性肾脏疾病的患病率约为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，但许多慢性肾病患者仍进展为终末期肾病。氧化应激增加是慢性肾脏疾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)基因的一种常见的缺失变体，即GSTM1零等位基因(GSTM1(0))，会导致GSTM1酶活性降低，并与更高水平的氧化应激有关。GSTM1属于GSTs超家族，是II相抗氧化酶，受核因子红系2相关因子2(NRF2)调节。一般来说，十字花科蔬菜，特别是西兰花，富含葡萄糖萝卜素，这是一种萝卜硫素的前体，已被证明通过激活Nrf2对氧化损伤具有保护作用。这篇综述将重点介绍GSTM1缺乏在高血压和肾脏疾病中的作用以及它对十字花科蔬菜对肾脏损伤和疾病进展的影响的最新人类和动物研究，阐明基因和环境交互作用的重要性以及在肾脏疾病治疗中靶向精确药物的潜力。
In the United States, the prevalence of chronic kidney disease in adults is ~14%. The mainstay of therapy for CKD are angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but many chronic kidney disease patients 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 (GSTM1) gene, the GSTM1 null allele (GSTM1(0)), 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 nuclear factor erythroid 2-related factor 2 (Nrf2). 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.