Genetics
CETP D442G mutation more than doubles vascular disease prevalence in dialysis patients, but only when HDL cholesterol is already low (Kidney Int Suppl 1999)
Original title: A common mutation of cholesteryl ester transfer protein gene in dialysis patients
Since decreased HDL-cholesterol is an independent vascular disease (VD) risk factor in hemodialysis patients, and the CETP D442G mutation raises HDL-cholesterol while potentially impairing reverse cholesterol transport, this study compared D442G genotype distribution and postprandial lipids between hemodialysis patients with and without VD in 414 patients. Total cholesterol and HDL-cholesterol did not differ between mutation carriers and non-carriers overall, or between VD and non-VD groups. However, patients with HDL-cholesterol below 45 mg/dL had significantly higher VD prevalence than those above (26.0% vs 15.2%, P less than 0.01), and within this low-HDL subgroup, D442G carriers had significantly higher VD prevalence than non-carriers (54.5% vs 24.4%, P less than 0.05). In this subgroup, VD-affected carriers had higher total cholesterol and atherogenic index than non-VD carriers, the opposite pattern seen in non-carriers. The authors conclude D442G may be a risk factor for atherosclerotic complications specifically in dialysis patients with low HDL-cholesterol.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.