The relationship between peroxisome proliferator-activated receptor-gamma and renin: a human genetics study.

ABSTRACT: 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.The aim was to examine the relationship between the PPARgamma gene and plasma renin activity (PRA) levels in human hypertension.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).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).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.

SUBMITTER: Underwood PC 

PROVIDER: S-EPMC2936061 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature