Kidney and Dialysis Research Laboratory, Division of Nephrology, Department of Medicine, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
Kidney Int. 2012 Oct;82(8):909-19. doi: 10.1038/ki.2012.235. Epub 2012 Jun 27.
Myeloperoxidase (MPO) is a lysosomal enzyme that may be involved in oxidative stress-mediated kidney injury. Using a two-step approach, we measured the association of four polymorphisms across the length of the MPO gene with systemic markers of oxidative stress: plasma MPO and urinary 15-F(2t)-isoprostane levels. Adverse outcomes were measured in a primary cohort of 262 adults hospitalized with acute kidney injury, and a secondary cohort of 277 adults undergoing cardiac surgery with cardiopulmonary bypass and at risk for postoperative acute kidney injury. Dominant and haplotype multivariable logistic regression analyses found a genotype-phenotype association in the primary cohort between rs2243828, rs7208693, rs2071409, and rs2759 MPO polymorphisms and both markers of oxidative stress. In adjusted analyses, all four polymorphic allele groups had 2-3-fold higher odds for composite outcomes of dialysis or in-hospital death or a composite of dialysis, assisted mechanical ventilation, or in-hospital death. The MPO T-G-A-T haplotype copy-number was associated with lower plasma MPO levels and lower adjusted odds for the composite outcomes. Significant but less consistent associations were found in the secondary cohort. In summary, our two-step genetic association study identified several polymorphisms spanning the entire MPO gene locus and a common haplotype marker for patients at risk for acute kidney injury.
髓过氧化物酶（MPO）是一种溶酶体酶，可能参与氧化应激介导的肾损伤。我们采用两步法，测量了 MPO 基因全长上的四个多态性与系统性氧化应激标志物：血浆 MPO 和尿 15-F(2t)-异前列腺素水平的相关性。在一个包含 262 名急性肾损伤住院患者的主要队列和一个接受体外循环心脏手术并存在术后急性肾损伤风险的 277 名成人的次要队列中，对不良结局进行了测量。在主要队列中，rs2243828、rs7208693、rs2071409 和 rs2759MPO 多态性与两种氧化应激标志物之间存在 rs2243828、rs7208693、rs2071409 和 rs2759MPO 多态性与两种氧化应激标志物之间的基因型-表型关联。在调整分析中，所有四个多态性等位基因组发生透析或住院死亡或透析、辅助机械通气或住院死亡复合结局的几率都高出 2-3 倍。MPO T-G-A-T 单倍型拷贝数与血浆 MPO 水平降低和调整后复合结局几率降低有关。在次要队列中发现了一些有意义但不太一致的关联。总之，我们的两步遗传关联研究确定了几个跨越整个 MPO 基因座的多态性和一个急性肾损伤风险患者的常见单倍型标记。
