PPARgamma gene C161T substitution is associated with reduced risk of coronary artery disease and decreased proinflammatory cytokine expression.

Abstract

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.

• Authors: Yu Liu, Zuyi Yuan, Yan Liu, Jijun Zhang, Ping Yin, Dongqi Wang, Yanni Wang, Chiharu Kishimoto, Aiqun Ma
• Journal: American heart journal (Am Heart J) Vol. 154 Issue 4 Pg. 718-24 (Oct 2007) ISSN: 1097-6744 [Electronic] United States
• PMID: 17892998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• PPAR gamma
• Tumor Necrosis Factor-alpha
• Matrix Metalloproteinase 9

Topics

• Aged
• Angina Pectoris, Variant (blood, genetics)
• Asian People (genetics)
• Chest Pain (genetics)
• Coronary Disease (genetics)
• Disease Progression
• Female
• Genotype
• Humans
• Logistic Models
• Male
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Myocardial Infarction (blood, genetics)
• PPAR gamma (genetics)
• Polymorphism, Genetic (physiology)
• Polymorphism, Restriction Fragment Length
• Risk Assessment
• Syndrome
• Tumor Necrosis Factor-alpha (blood)