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

TY - JOUR

T1 - A myeloperoxidase promoter polymorphism is independently associated with mortality in patients with impaired left ventricular function.

AU - Rudolph, Volker

AU - Rudolph, Tanja Katharina

AU - Kubala, Lukas

AU - Clauberg, Navina

AU - Maas, Renke

AU - Pekarova, Michaela

AU - Klinke, Anna

AU - Lau, Denise

AU - Szöcs, Katalin

AU - Meinertz, Thomas

AU - Böger, Rainer

AU - Baldus, Stephan

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 47

SP - 1584

EP - 1590

JO - FREE RADICAL BIO MED

JF - FREE RADICAL BIO MED

SN - 0891-5849

IS - 11

M1 - 11

ER -