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

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

Author information

1
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115, USA. punderwood1@partners.org

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.

PMID:
20631015
PMCID:
PMC2936061
DOI:
10.1210/jc.2010-0270
[Indexed for MEDLINE]
Free PMC Article

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