Cys327Cys polymorphism of the PAPP-A gene (pregnancy associated plasma protein A) is related to mortality of long term hemodialysis patients
Abstract
Objectives: 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. Design and methods: The studied group consisted of 464 subjects -319 long term hemodialysis patients (183 men, 136 women, 62 +/- 14 years) and 145 controls (65 men, 80 women, 49 +/- 14 years).
A subgroup of 211 hemodialysis patients (118 men, 93 women, 63 +/- 13 years) was prospectively followed up for 4.5 years. 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.