Genetic and gene expression studies implicate renin and endothelin-1 in edema caused by peroxisome proliferator-activated receptor gamma agonists

What Was Tested

Researchers studied Endothelin-1 in this randomized controlled trial publication.

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists can cause peripheral edema in susceptible individuals.

To investigate the mechanistic basis underlying this adverse event, the researchers performed a candidate gene analysis of patients enrolled in clinical trials of muraglitazar, an investigational PPARalpha/gamma dual agonist, and developed a cell culture-based gene expression assay and nonhuman primate model of edema to study the edemagenic properties of PPARgamma agonists.

Chi-square and logistic regression analyses were used to test for association with edema.

Who Took Part

According to the abstract, 730 participants were involved.

PubMed tags the participants as both men and women.

A total of 213 single nucleotide polymorphisms (SNPs) in 63 genes were genotyped in 730 participants.

How the Study Was Run

In design terms this was a randomized study.

Random assignment meant chance, not the researchers, decided who got Endothelin-1 and who got the comparison, which limits bias.

Transcriptional responses to PPARgamma agonists were evaluated in Calu-6 cells using quantitative real-time PCR.

Male Cynomolgus monkeys were treated with PPAR agonists and were evaluated for edema using MRI.

What Was Measured

PubMed files the paper under topics including Diabetes Mellitus, Type 2, Edema, Endothelin-1, Gene Expression Regulation, Glycine, Macaca fascicularis and Oxazoles.

What This Means in Plain Language

The paper is a randomized study of Endothelin-1 in 730 participants.

With several hundred people or more, it is a fairly large study for this kind of research.

Its findings take up roughly 5 sentences of the abstract and are left out here on purpose; the source paper is the place to read them.

The publication is from 2008 (Pharmacogenetics and genomics), a journal based in United States.

More context: the Endothelin-1 compound page, all human trials.