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

J Clin Endocrinol Metab. 2010 Sep;95(9):E75-9. doi: 10.1210/jc.2010-0270. Epub 2010 Jul 14.

Abstract

Context: 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.

Objective: The aim was to examine the relationship between the PPARgamma 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 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).

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 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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans / genetics
  • Alleles
  • Edema / blood
  • Edema / genetics
  • Edema / metabolism
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetics, Medical
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Hypertension / blood*
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Male
  • Middle Aged
  • PPAR gamma / genetics*
  • Polymorphism, Single Nucleotide
  • Renin / blood*
  • Renin / metabolism
  • Skin Diseases / blood
  • Skin Diseases / genetics
  • Skin Diseases / metabolism

Substances

  • PPAR gamma
  • Renin