title: A myeloperoxidase promoter polymorphism is independently associated with mortality in patients with impaired left ventricular function.
abstract: 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.
authors.affiliation: Department of Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany. v.rudolph@uke.de
authors.forename: Volker
authors.initials: V
authors.lastname: Rudolph
authors.forename: Tanja K
authors.initials: TK
authors.lastname: Rudolph
authors.forename: Lukas
authors.initials: L
authors.lastname: Kubala
authors.forename: Navina
authors.initials: N
authors.lastname: Clauberg
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarova
authors.forename: Anna
authors.initials: A
authors.lastname: Klinke
authors.forename: Denise
authors.initials: D
authors.lastname: Lau
authors.forename: Katalin
authors.initials: K
authors.lastname: Szöcs
authors.forename: Thomas
authors.initials: T
authors.lastname: Meinertz
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000503:physiopathology
chemical_list: D009195:Peroxidase