The relationship between peroxisome proliferator-activated receptor-γ and renin: A human genetics study

Abstract

Context: Peroxisome proliferator-activated receptor γ (PPARγ) agonists often cause volume retention and edema. A relationship between PPARγ and renin may play a role in this process. Objective: The aim was to examine the relationship between the PPARγ gene and plasma renin activity (PRA) levels in human hypertension. Design, Participants, and Measures: 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 PPARγ 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·min). Results: 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). Conclusions: These results demonstrate the first known association between a PPARγ single nucleotide polymorphism and alterations in PRA levels in humans with hypertension. This link between PPARγ and renin raises the possibility of a genetically based mechanism for the increased volume retention and edema in some users of PPARγ agonists. Copyright © 2010 by The Endocrine Society.