Journal Article

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

Philipp Eller, Kathrin Hochegger, Gudrun M. Feuchtner, Emanuel Zitt, Ivan Tancevski, Andreas Ritsch, Florian Kronenberg, Alexander R. Rosenkranz, Josef R. Patsch and Gert Mayer

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 1, pages 321-327
Published in print January 2008 | ISSN: 0931-0509
Published online September 2007 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfm566
Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure

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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

Journal Article.  4146 words.  Illustrated.

Subjects: Nephrology

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