Role of the endothelin-1 gene locus for renal impairment in the general nondiabetic population

SJ Pinto-Sietsma, SM Herrmann, K Schmidt-Petersen, T Hiu, HL Hillege, WMT Janssen, D De Zeeuw, P De Jong, R Kreutz*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

A decreased GFR in the range of mild renal insufficiency and an increased urinary albumin excretion (UAE) rate in the range of microalbuminuria are important cardiovascular risk factors. Endothelin-1 (ET-1) has been suggested to be a major disease promoting factor in renal disease. The role of the ET-1 gene locus (EDN1) for renal function in the general nondiabetic population was evaluated. To explore the overall relevance of EDN1, two suitable single-nucleotide polymorphisms, EDN1 K198N and EDN1 T-1370G, were selected, and haplotype analysis was performed. Determined were genotypes in 7291 nondiabetic subjects from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Genetic analysis was related to UAE and GFR as continuous variables and to microalbuminuria and diminished filtration as dichotomous traits. In a logistic regression analysis, no significant higher risk for increased UAE, microalbuminuria, decreased GFR, or diminished filtration could be observed for either single-nucleotide polymorphism separately. Haplotype analysis revealed that individuals with the homozygous G-N haplotype (compound EDN1 - 1370GG/198NN genotype) have a lower GFR than the remaining subjects (P <0.05) and exhibit a significant higher risk for the presence of a diminished filtration (relative risk, 2.4; 95% confidence interval, 1.07 to 5.33; P <0.05). Further analysis demonstrated no association between this haplotype and UAE or plasma ET-I levels. Although a functional relevance of the EDN1 G-N haplotype itself remains unclear, the data demonstrate that genetic variation at the EDN1 locus has a significant effect on glomerular filtration but not on UAE in the general nondiabetic population.

Original languageEnglish
Pages (from-to)2596-2602
Number of pages7
JournalJournal of the American Society of Nephrology
Volume14
Issue number10
DOIs
Publication statusPublished - Oct-2003

Keywords

  • URINARY ALBUMIN EXCRETION
  • HAPLOTYPE INFERENCE
  • BLOOD-PRESSURE
  • DISEASE
  • HYPERTENSION
  • POLYMORPHISMS
  • PROGRESSION
  • DISSECTION

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