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


METHODS
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.
Underwood
Patricia C
PC
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115, USA. punderwood1@partners.org
Sun
Bei
B
Williams
Jonathan S
JS
Pojoga
Luminita H
LH
Chamarthi
Bindu
B
Lasky-Su
Jessica
J
Raby
Benjamin A
BA
Hopkins
Paul N
PN
Jeunemaitre
Xavier
X
Brown
Nancy J
NJ
Adler
Gail K
GK
Williams
Gordon H
GH
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D004487:Edema / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005826:Genetics, Medical; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012083:Renin / Q000097:blood* / Q000378:metabolism; D012871:Skin Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics
D047495:PPAR gamma; D012083:Renin