Differential effect of two common polymorphisms in the cholesteryl ester transfer protein gene on low-density lipoprotein particle size

This study was performed to determine the relationship between the two common polymorphisms of cholesteryl ester transfer protein (CETP) gene and LDL size in Japanese individuals. The LDL size was determined by gradient gel electrophoresis in 136 patients undergoing routine check-ups. The presence of two polymorphisms (1405V and Taq1B) was determined using PCR-based methods. The VV genotype for the 1405V polymorphism was associated with both a lower plasma CETP concentration and a higher plasma HDL-C concentration. Further, the LDL size in patients with the VV genotype was significantly smaller than that in patients with the II + IV genotype (26.0 +/- 0.8 vs. 26.3 +/- 0.7 nm, P < 0.05). Although the 132132 genotype for the Taq1B polymorphism was also associated with both a lower plasma CETP concentration and a higher plasma HDL-C concentration, it had no effect on the LDL size (26.2 +/- 0.7 vs. 26.3 +/- 0.8 nm, P = 0.73). Stepwise multiple regression analysis revealed that the VV genotype, as well as plasma TG concentration, age, HbAlc concentration, and BMI, were determinants of LDL size, while no significant relationships were seen between any of the Taq1B polymorphisms and LDL size. These data suggest that the 1405V polymorphism but not the Taq1B polymorphism may be responsible for the distribution of LDL size. This may explain the differential effects of these two polymorphisms on the risk of CHD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.