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- Title
The relationship between peroxisome proliferator-activated receptor-gamma and renin: a human genetics study.
- Authors
Underwood, Patricia C; Sun, Bei; Williams, Jonathan S; Pojoga, Luminita H; Chamarthi, Bindu; Lasky-Su, Jessica; Raby, Benjamin A; Hopkins, Paul N; Jeunemaitre, Xavier; Brown, Nancy J; Adler, Gail K; Williams, Gordon H
- Abstract
<bold>Context: </bold>Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists often cause volume retention and edema. A relationship between PPARgamma and renin may play a role in this process.<bold>Objective: </bold>The aim was to examine the relationship between the PPARgamma gene and plasma renin activity (PRA) levels in human hypertension.<bold>Design, Participants, and Measures: </bold>A candidate gene association study was conducted with two distinct groups of human participants: Caucasian hypertensives (n = 395) and African-American hypertensives (n = 55). Single nucleotide polymorphisms of the PPAR(Upsilon) gene were analyzed. Phenotype studies were conducted after participants consumed a low-salt diet (10 mmol/d) for 7 d and included PRA and aldosterone measurements before and after a 60-min angiotensin II infusion (3 ng/kg x min).<bold>Results: </bold>Participants homozygous for the minor allele of rs2959272 (CC) had significantly higher PRA levels at baseline (P = 0.016) than major allele carriers (AA, AC) in Caucasian-hypertensive participants. The association of the C allele carrier status with increased PRA levels was replicated in the group of African-American hypertensive participants (P = 0.027). The Fisher's combined P value for both observations was significant (P = 0.002).<bold>Conclusions: </bold>These results demonstrate the first known association between a PPARgamma single nucleotide polymorphism and alterations in PRA levels in humans with hypertension. This link between PPARgamma and renin raises the possibility of a genetically based mechanism for the increased volume retention and edema in some users of PPARgamma agonists.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2010, Vol 95, Issue 9, pE75
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2010-0270