Background: In patients on maintenance hemodialysis, a decreased concentration of high-density lipoprotein cholesterol (HDL-C) is an apparent independent risk factor for vascular disease (VD). A common missense mutation of cholesteryl ester transfer protein (CETP) gene, D442G (Asp442 to Gly), increases HDL-C levels, but the mutation may also diminish the activity of reverse cholesterol transport.
Methods: We compared the genotype distribution of the D442G polymorphism and postprandial serum lipid levels between patients with and without VD in 414 hemodialysis patients.
Results: Serum levels of total cholesterol and HDL-C did not differ in patients with the mutation [group M (+)] and without the mutation [group M (-)] and in patients with and without VD. However, patients with below median HDL-C levels (< 45 mg/dl) had a significantly higher prevalence of VD than those with above median HDL levels (26.0 vs. 15.2%, P < 0.01). Moreover, in this low-HDL-C subgroup, group M (+) patients had a significantly higher prevalence of VD than group M (-) patients (54.5 vs. 24.4%, P < 0.05). In the subgroup, group M (+) patients with VD had higher levels of total cholesterol and a higher atherogenic index than those without VD, whereas group M (-) patients with VD had lower levels of total cholesterol and a lower atherogenic index than those without VD.
Conclusions: The D442G mutation may be a risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl. Atherogenic lipid profiles may promote atherosclerosis in the patients with the mutation, but not in those with no mutation.