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

Underwood PC, Sun B, Williams JS, Pojoga LH, Chamarthi B, Lasky-Su J, Raby BA, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams GH
J Clin Endocrinol Metab. 2010 95 (9): E75-9

PMID: 20631015 · PMCID: PMC2936061 · DOI:10.1210/jc.2010-0270

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.

MeSH Terms (19)

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

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