PPARgamma gene C161T substitution is associated with reduced risk of coronary artery disease and decreased proinflammatory cytokine expression.
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor implicated in the expression of proinflammatory cytokines in atheroma-associated cells, and the expression of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMPs), represents a critical step in atherogenesis and atherosclerosis. In this study, we test the hypothesis of whether a polymorphism corresponding to C161T substitution in exon 6 of the PPARgamma gene may affect the expression of proinflammatory cytokines and the onset of coronary artery diseases (CADs) in a Chinese population.


METHODS
We have studied distribution of the PPARgamma C161T substitution at exon 6 in 247 patients with CAD and 214 patients with chest pain syndrome. The plasma concentrations of MMP-9 and TNF-alpha were measured by enzyme-linked immunosorbent assay.


RESULTS
The results showed that the frequencies of the CC, CT, and TT genotypes were 61.9%, 34.0%, and 4.1% in CAD, and 51.4%, 45.3%, and 3.3% in chest pain syndrome, respectively. There was a significant association between the PPARgamma C161T polymorphism and CAD. The T allele carriers (CT + TT) had significantly reduced CAD risk compared with the CC homozygotes (odds ratio 0.547, 95% CI 0.327-0.831, P = .012) in a logistic regression model after controlling known independent factors for CAD. The CC homozygotes also had increased MMP-9 and TNF-alpha levels compared with T allele carriers. Moreover, the CC homozygotes were more susceptible to acute coronary syndrome than T allele carriers.


CONCLUSIONS
PPARgamma C161T polymorphism was associated with angiographically documented CAD in a Chinese population. The T allele of the PPARgamma gene might have a protective effect on the progression of CAD and reduce the onset of acute coronary syndrome, which might be associated with the decreased expression of MMP-9 and TNF-alpha in patients with CAD.
Liu
Yu
Y
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Yuan
Zuyi
Z
Liu
Yan
Y
Zhang
Jijun
J
Yin
Ping
P
Wang
Dongqi
D
Wang
Yanni
Y
Kishimoto
Chiharu
C
Ma
Aiqun
A
D000368:Aged; D000788:Angina Pectoris, Variant / Q000097:blood / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002637:Chest Pain / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology*; D012150:Polymorphism, Restriction Fragment Length; D018570:Risk Assessment; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9