Abstract
BackgroundCardiovascular (CV) complications are the main cause of death in end-stage renal disease (ESRD) patients. The high CV risks are attributable to the additive effects of multiple factors. Endothelin (EDN) is a potent vasoconstrictor and plays a role in regulating vascular homeostasis. However, whether variants of the EDN gene are associated with risks of CV events is not known. We conducted a study to investigate associations of variants of the EDN gene with CV events in ESRD patients.MethodsA cohort of 190 ESRD patients was recruited, and 19 tagged single-nucleotide polymorphisms within the EDN gene family were selected for genotyping through a TaqMan assay. Data on clinical characteristics and hospitalizations for CV events were collected. Associations of genetic variants of the EDN gene with CV events were analyzed.ResultsIn this cohort, 62% (n = 118) of patients were hospitalized for a CV event. The EDN1 rs4714384 (CC/TC vs. TT) polymorphism was associated with an increased risk of a CV event after multiple testing (p < 0.001). Further functional exploration showed that it was a quantitative trait locus which may significantly alter gene expression in the tibial artery.ConclusionsEDN1 rs4714384 is very likely an important biomarker of CV events in ESRD patients.
Highlights
Cardiovascular (CV) complications are the main cause of death in end-stage renal disease (ESRD) patients
End-stage renal disease (ESRD) patients have a high risk of mortality, and 50% of these deaths are from cardiovascular (CV) complications [1]
Pre-existing CV events were found in 43 patients with more than 83% due to congestive heart failure (CHF) (n = 16, 37%) and coronary artery disease (CAD) (n = 20, 47%)
Summary
Cardiovascular (CV) complications are the main cause of death in end-stage renal disease (ESRD) patients. Whether variants of the EDN gene are associated with risks of CV events is not known. We conducted a study to investigate associations of variants of the EDN gene with CV events in ESRD patients. Associations of genetic variants of the EDN gene with CV events were analyzed. The EDN1 rs4714384 (CC/TC vs TT) polymorphism was associated with an increased risk of a CV event after multiple testing (p < 0.001). End-stage renal disease (ESRD) patients have a high risk of mortality, and 50% of these deaths are from cardiovascular (CV) complications [1]. It may contribute to the excess risk of sudden cardiac death and indicates poor survival in ESRD patients [3]. The exact mechanisms responsible for the excess CV risk in ESRD patients are not well understood
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