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Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 1507270, 7 pages
http://dx.doi.org/10.1155/2016/1507270
Research Article

A Genetic Biomarker of Oxidative Stress, the Paraoxonase-1 Q192R Gene Variant, Associates with Cardiomyopathy in CKD: A Longitudinal Study

1Department of Nephrology, University Hospital of Ioannina, 45110 Ioannina, Greece
2Laboratory of Clinical Genetics and Human Reproduction, Medical School University of Ioannina, 45110 Ioannina, Greece
3CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, 89124 Reggio Calabria, Italy
4Department of Cardiology, University Hospital of Ioannina, 45110 Ioannina, Greece
5Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
6Department of Internal Medicine, University Hospital of Ioannina, 45110 Ioannina, Greece
7Department of Nephrology, General Hospital “Papageorgiou” of Thessaloniki, 564 29 Thessaloniki, Greece

Received 11 March 2016; Revised 24 April 2016; Accepted 5 May 2016

Academic Editor: José Pedraza-Chaverri

Copyright © 2016 E. Dounousi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Oxidative stress is a hallmark of CKD and this alteration is strongly implicated in LV hypertrophy and in LV dysfunction. Methods and Patients. We resorted to the strongest genetic biomarker of paraoxonase-1 (PON1) activity, the Q192R variant in the PON1 gene, to unbiasedly assess (Mendelian randomization) the cross-sectional and longitudinal association of this gene-variant with LV mass and function in 206 CKD patients with a 3-year follow-up. Results. The R allele of Q192R polymorphism associated with oxidative stress as assessed by plasma 8-isoPGF2α () and was dose-dependently related in a direct fashion to LVMI (QQ: 131.4 ± 42.6 g/m2; RQ: 147.7 ± 51.1 g/m2; RR: 167.3 ± 41.9 g/m2; ) and in an inverse fashion to systolic function (LV Ejection Fraction) (QQ: 79 ± 12%; RQ: 69 ± 9%; RR: 65 ± 10% ). On longitudinal observation, this gene variant associated with the evolution of the same echocardiographic indicators [LVMI: 13.40 g/m2 per risk allele, ; LVEF: −2.96% per risk allele, ]. Multivariate analyses did not modify these associations. Conclusion. In CKD patients, the R allele of the Q192R variant in the PON1 gene is dose-dependently related to the severity of LVH and LV dysfunction and associates with the longitudinal evolution of these cardiac alterations. These results are compatible with the hypothesis that oxidative stress is implicated in cardiomyopathy in CKD patients.