Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia: comparison among CETP/TaqIB genotype subgroups.
We investigated the effects of HMG-CoA reductase inhibitors (statins) on the activity and concentration of plasma cholesterol ester transfer protein (CETP) in 30 hypercholesterolemic patients. Patients were divided into three groups according to TaqIB polymorphism of the CETP gene. The activity (158 +/- 23% control, mean +/- SEM) and concentration (4.1 +/- 1.0 mg/l) of plasma CETP were significantly (p < 0.005) higher in the subjects with the B1B1 genotype than B2B2 genotype (106 +/- 25% and 2.5 +/- 1.1 mg/l, respectively). Plasma CETP activity and concentration levels in the B1B2 group were intermediate between those of the B1B1 and B2B2 groups, and significantly (p < 0.05) low compared with the B1B1 group.Both the activity and concentration of plasma CETP were positively correlated with the LDL-cholesterol concentration (r = 0.608, p < 0.0005 and r = 0.552, p < 0.005, respectively). The administration of statins significantly reduced not only the activity (p < 0.01) but also the concentration (p < 0.05) of plasma CETP in hypercholesterolemic patients. Taken together, we confirmed that statins would be effective in increasing HDL levels in Japanese B1B1 carriers, because of a lower concentration of HDL cholesterol and higher level of plasma CETP compared to the other genotypes. The genetic variation in the CETP gene may be one important factor in designing better treatments.
Kotake
Hidetoshi
H
Division of Endocrinology and Metabolism, Tohoku University School of Medicine, Miyagi, Japan.
Sekikawa
Akihiro
A
Tokita
Yoshihisa
Y
Ishigaki
Yasushi
Y
Oikawa
Shinichi
S
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors