Background: Peroxisome proliferator activated receptor alpha (PPARalpha) regulates genes involved in lipoprotein metabolism, hemostasis, and inflammation. It thus represents a candidate gene for the risk of dyslipidemia, atherosclerosis, and coronary heart disease (CHD). Nonesterified fatty acids are PPARalpha ligands and their levels are increased in patients with diabetes mellitus type 2 (DM-2). The effects of the polymorphism of PPARalpha on plasma lipids and atherosclerosis development have been until now contradictory. The present study was performed to evaluate the association between the PPARalpha polymorphism L162V and the presence of dyslipidemia and/or atherosclerotic disease in patients with DM-2 in comparison with nondiabetic controls.
Methods and results: We determined this polymorphism in 404 subjects with DM-2 and in 438 age and sex-matched nondiabetic controls. The V allele was present in 9.4% of patients with DM-2 and in 11.4% of the control group (P =.34). There was no significant association between the presence of the polymorphism and body mass index. There was no association between the polymorphism and lipoprotein concentrations in either group, independent of lipid-lowering therapy. In patients with DM-2, there was a trend towards a lower prevalence of atherosclerosis in carriers versus noncarriers of the V allele (P =.0837). In the control group, the presence of the V allele was not associated with an altered prevalence of atherosclerotic disease (P =.45). Likewise, there was a trend towards lower CHD prevalence in carriers versus noncarriers of the V allele (P =.0622). The presence of the polymorphism was not associated with CHD in the control group (P =.80).
Conclusions: The data suggest that the PPARalpha polymorphism L162V might protect against the development of atherosclerosis or CHD in patients with DM-2. The absence of an association between the polymorphism and plasma lipoprotein concentrations may suggest that these protective effects are exerted directly on the arterial wall.