Lack of association between peroxisome proliferator-activated receptor-γ-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus

Objective: Recent evidence indicates that peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed at high levels in foam cells of atherosclerotic lesions, that PPARgamma agonists may directly modulate vessel wall function and that mutations in the PPARgamma-2 gene are associated with a reduced risk of coronary artery disease. Methods: We investigated whether known variants in the PPARgamma-2 gene are associated with the occurrence of coronary heart disease (CHD) in 365 patients with type 2 diabetes, prospectively characterised for the presence or absence of CHD. The Pro115Gln, Pro12Ala, Pro467Leu, Val290Met mutations and two polymorphisms C478T and C161T of the PPARgamma-2 gene were examined using PCR, denaturing gradient gel electrophoresis and direct sequencing. Results: The distribution of the Pro12Ala, Alal2Ala, C161T and T161T variants was not significantly different between patients with and without CHD, independent of the gender. The Pro12Ala (P = 0.011) and the Ala12Ala (P = 0.006) variant were associated with a higher body mass index (BMI) compared with the Pro12Pro genotype. A multiple logistic regression analysis introducing the typical risk factors for CHD (age, sex, hypertension, smoking, BMI > 26 kg /m(2), elevated low density lipoprotein cholesterol and haemoglobin A(1)c > 7%) identified age > 60, male gender, hypertension and a higher BMI, but not the PPARgamma-2 variants, as significant risk factors for CHD in our study groups. Conclusion: The PPARgamma-2 genotype was not associated with an increased or reduced risk of the occurrence of CHD and can therefore not be regarded as an independent risk factor for CHD in patients with diabetes mellitus.