Gene–gene interaction of PPARγ and ApoE affects coronary heart disease risk

Abstract

Background: Apolipoprotein ε4 has been proposed as a genetic predictor for CHD. Peroxisome proliferator-activated receptors (PPAR), a recent identified nuclear transcription factor, is involved in regulation of many target genes and plays an important role in lipid metabolism, insulin sensitivity, obesity and atherosclerosis. PPARγ gene polymorphisms may affect the profile of CHD-related risk factors. Hypothesis: Interaction between PPARγ gene polymorphism and apoE polymorphisms affect the presence of CHD. Method: This is a case–control study, which enrolled 150 cases with CHD and 157 controls without CHD. Polymerase chain reaction-restricted fragments length polymorphism was used to determine the apoE genotype and PPARγ C161→T substitution. Results: ApoE ε4 allele was significantly more prevalent in CHD patients than in controls (13.05 vs. 7.35%, P<0.05). The apoE ε4 carries had significant higher LDL-C levels than other apoE carriers and this tendency could be modified by PPARγ CT genotype. ApoE genotype ε4 was an independent risk factor for CHD (OR=4.29, 95%CI: 1.6–11.48, P=0.004). A significant interaction between apoE ε4 and PPARγ CT genotype was detected with respect to the effect on CHD ( P=0.045). Conclusion: This is the first study to explore the effect of interaction between PPARγ C161→T variant and apoE ε4 genotype. The result exhibited an interaction effect of two genes on serum cholesterol level. The association of CHD to apoE genotype was subjected to the attenuation effect of PPARγ CT genotype.