Effect of a common mutation (D442G) of the cholesteryl ester transfer protein gene on lipids and lipoproteins in children

Cholesteryl ester transfer protein (CETP) is thought to regulate plasma HDL . Patients with CETP deficiency caused by mutation of the CETP gene [D442G; a missense mutation (Asp442 --> Gly)] have been reported to show high plas ma HDL levels. However, there are no data available on children with D442G. To determine the effects of plasma CETP and CETP gene mutation (D442G) on lipids and lipoproteins in children, we screened children by PCR and restri ction fragment length polymorphism analysis of the CETP gene. Plasma lipids , apolipoproteins, and CETP mass levels were also determined. In the curren t study, 22 children with D442G were found (21 heterozygotes and a homozygo te). A homozygous child showed high plasma HDL level and very low plasma CE TP mass. In heterozygous children, plasma concentrations of HDL cholesterol , apo A-I and apo A-II were not increased, whereas plasma CETP mass was sig nificantly decreased. Plasma CETP mass in heterozygous children was correla ted with plasma concentrations of total cholesterol, LDL cholesterol, and a po B. Plasma CETP mass in children without D442G was not correlated with th e plasma concentration of any lipid or apolipoprotein. All of these data su ggest that the D442G mutation, by itself, might not affect HDL metabolism i n children. The CETP mass required for efficient HDL-cholesteryl ester clea rance in children may be less than that in older subjects.