Candidate Gene Analysis of Mortality in Dialysis Patients

Tonia C Rothuizen; Gurbey Ocak; Jeffrey J W Verschuren; Friedo W Dekker; Ton J Rabelink; J Wouter Jukema; Joris I Rotmans

doi:10.1371/journal.pone.0143079

Candidate Gene Analysis of Mortality in Dialysis Patients

PLoS One. 2015 Nov 20;10(11):e0143079. doi: 10.1371/journal.pone.0143079. eCollection 2015.

Authors

Tonia C Rothuizen^{1

2}, Gurbey Ocak³, Jeffrey J W Verschuren⁴, Friedo W Dekker³, Ton J Rabelink^{1

2}, J Wouter Jukema^{4

5

6}, Joris I Rotmans^{1

2}

Affiliations

¹ Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
² Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
³ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.
⁶ The Interuniversity Cardiology Institute (ICIN), Utrecht, The Netherlands.

Abstract

Background: Dialysis patients have high cardiovascular mortality risk. This study aimed to investigate the association between SNPs of genes involved in vascular processes and mortality in dialysis patients.

Methods: Forty two SNPs in 25 genes involved in endothelial function, vascular remodeling, cell proliferation, inflammation, coagulation and calcium/phosphate metabolism were genotyped in 1330 incident dialysis patients. The effect of SNPs on 5-years cardiovascular and non-cardiovascular mortality was investigated.

Results: The mortality rate was 114/1000 person-years and 49.4% of total mortality was cardiovascular. After correction for multiple testing, VEGF rs699947 was associated with all-cause mortality (HR1.48, 95% CI 1.14-1.92). The other SNPs were not associated with mortality.

Conclusions: This study provides further evidence that a SNP in the VEGF gene may contribute to the comorbid conditions of dialysis patients. Future studies should unravel the underlying mechanisms responsible for the increase in mortality in these patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cardiovascular Diseases / etiology
Cardiovascular Diseases / mortality*
Cardiovascular Diseases / pathology
Dialysis / adverse effects*
Endothelium / metabolism
Endothelium / pathology
Female
Genetic Association Studies
Humans
Inflammation / complications
Inflammation / genetics
Inflammation / pathology
Male
Middle Aged
Polymorphism, Single Nucleotide
Renal Insufficiency, Chronic / complications
Renal Insufficiency, Chronic / genetics*
Renal Insufficiency, Chronic / therapy
Vascular Endothelial Growth Factor A / genetics*
Vascular Remodeling / genetics

Substances

VEGFA protein, human
Vascular Endothelial Growth Factor A

Grants and funding

JWJ was funded by grants from the Interuniversity Cardiology Institute of the Netherlands (ICIN), the European Community Framework KP7 Programme under grant agreement [n° HEALTH-F2-2009-223004], the Center for Medical Systems Biology (CMSB), a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NWO) and the Netherlands Consortium for Healthy Ageing (NCHA). The funders had no role in study design, data collection and analysis, decision to publish or the preparation of the manuscript. TCR and JR were supported by the research program of the BioMedical Materials institute (P3.03 DialysisXS), co-funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation.