CETP gene mutation (D442G) increases low-density lipoprotein particle size in patients with coronary heart disease

Abstract

Background: Small, dense low-density lipoprotein (LDL) in subjects with the atherogenic pattern B has been established as a risk factor of atherosclerosis. Cholesteryl ester transfer protein (CETP) plays an important role in the transfer and exchange of cholesteryl esters and triglycerides between the lipoprotein classes of human plasma. It has been shown that CETP can also change the particle size of high-density lipoprotein (HDL) and LDL subfractions in vitro. Previous clinical studies about CETP gene mutations mainly focused on abnormalities in HDL, few involved those in LDL. Objectives: To investigate the effect of the D442G mutation in the CETP gene on major peak size of LDL particles in patients with coronary heart diseases (CHD). Methods: D442G mutation in the CETP gene was detected using the PCR-RFLP. LDL particles sizes were analyzed by 2–16% nondenaturing polyacrylamide gradient gels in CHD patients with D442G mutation in the CETP gene. Results: Six heterozygotes and one homozygote were found to have the D442G mutation among 200 CHD patients. The frequency of this mutation was 3.5%. The major peak size of LDL in patients with gene mutation ( n=7) was significantly larger than that in patients without the mutation ( n=40) (26.92±0.79 nm vs. 25.71±0.66 nm, respectively; P<0.01). All the patients with the gene mutation expressed pattern A, whereas only about half of the patients without the mutation expressed this pattern. The patients with gene mutation had decreased plasma CETP concentration, while increased concentration of HDL-C and apolipoprotein A-I compared with controls. Conclusions: CETP gene mutation (D442G) increases LDL particle size. This suggests that CETP play an antiatherogenic role.