title: Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injury-related outcomes.
abstract: 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.
authors: 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.
authors: Mary C
authors: MC
authors: Perianayagam
authors: Hocine
authors: H
authors: Tighiouart
authors: Orfeas
authors: O
authors: Liangos
authors: Diana
authors: D
authors: Kouznetsov
authors: Ron
authors: R
authors: Wald
authors: Fangwen
authors: F
authors: Rao
authors: Daniel T
authors: DT
authors: O'Connor
authors: Bertrand L
authors: BL
authors: Jaber
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D001026:Coronary Artery Bypass / Q000009:adverse effects; D015237:Dinoprost / Q000031:analogs & derivatives; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D028421:Isoprostanes / Q000652:urine; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D011379:Prognosis
chemical_list: D005819:Genetic Markers; D028421:Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D009195:Peroxidase