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


OBJECTIVE
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.
Wang
Junjun
J
Department of Biochemistry, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305#, East Zhong Shan Road, Nanjing 210002, PR China. wangjj@jlonline.com
Qiang
Hongjuan
H
Chen
Daning
D
Zhang
Chunni
C
Zhuang
Yiyi
Y
D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006023:Glycoproteins; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010316:Particle Size; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008077:Lipoproteins, LDL