A myeloperoxidase promoter polymorphism is independently associated with mortality in patients with impaired left ventricular function

被引:17
作者
Rudolph, Volker [1 ]
Rudolph, Tanja K. [1 ]
Kubala, Lukas [2 ]
Clauberg, Navina [3 ]
Maas, Renke [4 ]
Pekarova, Michaela [2 ]
Klinke, Anna [1 ]
Lau, Denise [1 ]
Szoecs, Katalin [1 ]
Meinertz, Thomas [1 ]
Boeger, Rainer H. [3 ]
Baldus, Stephan [1 ]
机构
[1] Univ Heart Ctr Hamburg, Dept Cardiol, D-20246 Hamburg, Germany
[2] Acad Sci Czech Republ, Inst Biophys, CS-61265 Brno, Czech Republic
[3] Univ Hosp Hamburg Eppendorf, Dept Expt & Clin Pharmacol & Toxicol, D-20246 Hamburg, Germany
[4] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, Erlangen, Germany
关键词
Myeloperoxidase; Genetics; Heart failure; Survival; Free radicals; IMPLICATES MYELOPEROXIDASE; PROGNOSTIC VALUE; GENE VARIATION; DETERMINANTS; SPECIFICITY; PROGRESSION; FIBROSIS;
D O I
10.1016/j.freeradbiomed.2009.09.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Circulating levels of myeloperoxidase (MPO), a heme enzyme released upon activation of polymorphonuclear neutrophils, predict adverse outcome in patients with impaired left ventricular (LV) function. The MPO -463 G/A promoter polymorphism (rs 2333227) regulates MPO transcription, with the G allele being linked to increased protein expression. The aim of this study was to assess the prognostic information derived from the -463 G/A MPO polymorphism on outcomes of patients with impaired LV function. The -463 G/A promoter MPO genotype as well as MPO plasma levels were determined in 116 patients with impaired LV function. Patients were prospectively followed for a median of 1050 days. The GG genotype was associated with a decrease in overall survival (chi(2) 5.80; p=0.016). This association remained after multivariate adjustment for plasma levels of NT-proBNP, creatinine, hsCRP, and MPO; leukocyte count; and LV function (hazard ratio 3.16 (95% CI 1.17-8.53), p=0.024) and for classical cardiovascular risk factors (hazard ratio 2.88 (95% CI 1.13-7.33), p=0.026). Interestingly, we observed no association of the MPO polymorphism with total MPO protein concentration or MPO activity in plasma. The -463 G/A MPO polymorphism is linked to adverse clinical outcome of patients with impaired LV function. Further studies are needed to elucidate the value of this polymorphism for risk stratification. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:1584 / 1590
页数:7
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