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NDT Advance Access originally published online on September 10, 2007
Nephrology Dialysis Transplantation 2008 23(1):321-327; doi:10.1093/ndt/gfm566
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure

Philipp Eller1, Kathrin Hochegger2, Gudrun M. Feuchtner3, Emanuel Zitt2, Ivan Tancevski1, Andreas Ritsch1, Florian Kronenberg4, Alexander R. Rosenkranz2, Josef R. Patsch1 and Gert Mayer2

1Department of Internal Medicine, Division of General Internal Medicine, 2Department of Internal Medicine, Division of Nephrology, 3Department of Radiology, Innsbruck Medical University and 4Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology, Innsbruck Medical University, Austria

Correspondence to: Josef R. Patsch, Department of Internal Medicine, Division of General Internal Medicine, Anichstrasse 35, A-6020 Innsbruck, Austria. Email: josef.patsch{at}i-med.ac.at



  Abstract

Background. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates inorganic pyrophosphate, a solute that serves as an essential physiological inhibitor of calcification. Inactivating mutations of ENPP1 are associated with generalized arterial calcification of infancy. We hypothesized the ENPP1 K121Q variant to be associated with increased vascular calcification in patients with end-stage renal failure.

Subjects and methods. We recruited 79 patients with end-stage renal failure undergoing dialysis treatment and genotyped them for the ENPP1 K121Q polymorphism. Next, we matched to each patient with ENPP1 121KQ genotype (n = 15) a respective control with ENPP1 121KK genotype by gender, age, diabetes and duration of dialysis treatment. The matching ratio was 1 : 1. Severity of coronary calcification was quantified by computed tomography, and aortic stiffness was measured by pulse-wave analysis.

Results. Patients with ENPP1 121KQ genotype had a significantly higher coronary calcium score (1385 vs 94; n = 30; P = 0.033), and also a higher aortic pulse-wave velocity when compared to matched controls with ENPP1 121KK genotype (13.69 m/s vs 9.37 m/s; P = 0.003).

Conclusions. Taken together, our study suggests a potential role of the ENPP1 K121Q polymorphism in arterial calcification of patients with end-stage renal failure. Patients heterozygous for the ENPP1 K121Q polymorphism have higher coronary calcification scores and increased aortic stiffness, and may benefit from more intense treatment in order to prevent progression of arterial calcification.

Keywords: aortic stiffness; arterial calcification; insulin resistance; mineral metabolism; pulse-wave velocity; pyrophosphate

Received for publication: 23. 4.07
Accepted in revised form: 25. 7.07


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