Association of PPARgamma allelic variation, osteoprotegerin and abdominal aortic aneurysm.
OBJECTIVE
We have previously demonstrated high concentrations of the glycoprotein osteoprotegerin (OPG) in biopsies of abdominal aortic aneurysm (AAA), and demonstrated that ligation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) downregulates OPG in vitro and within a mouse model. The aims of this study were to assess the associations between circulating concentrations of OPG, polymorphisms of the gene encoding PPARgamma (PPARG), AAA presence and growth.


METHODS
Two genetic polymorphisms in PPARG were assessed in 4227 men, 699 of whom had an AAA. For 631 men, who had AAAs, maximum aortic diameter was monitored by yearly ultrasound for a median of 5 years. Plasma OPG was measured in 838 men, 318 of whom had an AAA.


RESULTS
Plasma concentrations of OPG were independently associated with AAA (adjusted odds ratio 1.38, 95% CI 1.10-1.72). The PPARG c.1347C > T polymorphism was associated with plasma concentrations of OPG (beta 0.12, P < 0.01). The PPARG c.34G > C polymorphism was weakly associated with AAA (adjusted odds ratio 1.28, 95% CI 1.01-1.61). PPARG c.1347C > T was associated with increased AAA growth (recessive model, P = 0.03).


CONCLUSIONS
Circulating concentrations of osteoprotegerin are associated with abdominal aortic aneurysm and with one peroxisome proliferator-activated receptor gamma gene polymorphism. Peroxisome proliferator-activated receptor gamma gene polymorphisms are weakly associated with abdominal aortic aneurysm presence and growth. Confirmation of these findings is required in other cohorts.
Moran
Corey S
CS
Vascular Biology Unit, School of Medicine and Dentistry, James Cook University, Townsville, Qld, Australia.
Clancy
Paula
P
Biros
Erik
E
Blanco-Martin
Bernardo
B
McCaskie
Pamela
P
Palmer
Lyle J
LJ
Coomans
Danny
D
Norman
Paul E
PE
Golledge
Jonathan
J
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001012:Aorta, Abdominal / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D053244:Osteoprotegerin / Q000097:blood* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
D053244:Osteoprotegerin; D047495:PPAR gamma; C506030:TNFRSF11B protein, human