title: Cys327Cys polymorphism of the PAPP-A gene (pregnancy associated plasma protein A) is related to mortality of long term hemodialysis patients.
abstract: OBJECTIVE
  PAPP-A is an independent mortality predictor of long term hemodialysis patients and a prognostic marker of acute coronary syndrome in general population. Cys327Cys PAPP-A polymorphism (SNP) (rs12375498) was found to be of significance in preeclampsia and the C allele of the PAPP-A C/G SNP (rs13290387) was defined as an independent risk factor for acute myocardial infarction. The aim of the study was to test the role of these PAPP-A SNPs in long term hemodialysis patients.
  
  
  METHODS
  The studied group consisted of 464 subjects - 319 long term hemodialysis patients (183 men, 136 women, 62±14years) and 145 controls (65 men, 80 women, 49±14years). A subgroup of 211 hemodialysis patients (118 men, 93 women, 63±13years) was prospectively followed up for 4.5years. During the follow up, 111 patients died, 51 of them due to cardiovascular events. PAPP-A SNPs were analyzed by DNA sequencing and serum PAPP-A was measured by TRACE.
  
  
  RESULTS
  Both SNPs were in Hardy-Weinberg equilibrium. Allelic and genotype frequencies did not differ between patients and controls and were not related to serum PAPP-A concentrations. Cys327Cys SNP was significant for patients' survival (HR (95% CI): 1.616 (1.110-2.353), nominal p=0.012, corrected p=0.036) while C/G SNP was not.
  
  
  CONCLUSIONS
  Our study shows for the first time the significance of Cys327Cys PAPP-A SNP (rs12375498) for overall mortality of long term hemodialysis patients. Although it does not influence the concentration of PAPP-A it still could affect the correct function of this enzyme which has to be clarified in further studies.
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University in Prague, Prague, Czech Republic. Electronic address: marta.kalousova@seznam.cz.
authors.forename: Marta
authors.initials: M
authors.lastname: Kalousová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University in Prague, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Jáchymová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University in Prague, Prague, Czech Republic.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Muravská
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University in Prague, Prague, Czech Republic.
authors.forename: Aleš A
authors.initials: AA
authors.lastname: Kuběna
authors.affiliation: Hemodialysis Centre, University Hospital Hradec Kralove, Czech Republic.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dusilová-Sulková
authors.affiliation: Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University in Prague, Prague, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Tesař
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University in Prague, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Zima
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics / Q000628:therapy; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics*; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors
chemical_list: D011266:Pregnancy-Associated Plasma Protein-A
keywords: Cardiovascular; Hemodialysis; PAPP-A; Polymorphism; Pregnancy-associated plasma protein A; Renal