The 161TT genotype in the exon 6 of the peroxisome-proliferator-activated receptor γ gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers

PPAR (peroxisome-proliferator-activated receptor) is a nuclear receptor. Activation of PPARgamma by its ligands could modulate gene transcription, thereby leading to multiple anti-atherogenic and fibrinolytic effects. However, the association between the 16IT allele in exon 6 of the PPARgamma gene and premature AMI (acute myocardial infarction) is not clear. We recruited 146 patients with premature AMI (onset age less than or equal to 50 years) and 146 controls. The C 16 1 T polymorphism was examined using PCR and restriction-fragment-length polymorphism. Plasma levels of Ab-ox-LDL (antibody against oxidized low-density lipoprotein) were measured in 27 male smokers, whose genotypes have been identified. The frequency of the PPARgamma TT genotype among patients with AMI was significantly higher than that in controls [ 13% compared with 5.5%; OR (95% CI) 2.7, (1.1-6.5), where OR and CI are odds ratio and confidence interval respectively]. This association was not observed in CC or CT genotypes. Using multivariate logistic regression analyses, we found that the homozygous TT genotype [OR (95% CI), 3.1 (1.2-7.9)], smoking [OR (95% CI), 3.5, (2.1-6.0)], hypertension [OR (95% CI), 3.6, (1.9-6.9)] and diabetes mellitus [OR (95% CI), 3.5 (1.5-8.4)] were independent risk factors for premature AMI. Plasma levels of Ab-ox-LDL were significantly higher in healthy volunteers with the TT genotype compared with those with the CC genotype (49.3 +/- 18.1 compared with 24.2 +/- 15.2 units/I respectively; P = 0.02). Therefore in our study we observed an association between the PPARgamma 161 TT genotype and premature AMI. Lipid peroxidation was significantly influenced by the 16 IT allele.