Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injuryrelated outcomes

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Abstract

Myeloperoxidase (MPO) is a lysosomal enzyme that may be involved in oxidative stressmediated 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 genotypephenotype 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 23-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. © 2012 International Society of Nephrology.

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Perianayagam, M. C., Tighiouart, H., Liangos, O., Kouznetsov, D., Wald, R., Rao, F., … Jaber, B. L. (2012). Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injuryrelated outcomes. Kidney International, 82(8), 909–919. https://doi.org/10.1038/ki.2012.235

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