Genetics
CETP B2B2 genotype raises HDL cholesterol and particle size specifically in women in the Columbia BioMarkers Study (Nutr Metab Cardiovasc Dis 2002)
Original title: Loci for CETP, LPL, LIPC, and APOC3 affect plasma lipoprotein size and sub-population distribution in Hispanic and non-Hispanic white subjects: the Columbia University BioMarkers Study
In forty Hispanic and 42 non-Hispanic white men plus 223 Hispanic and 53 non-Hispanic white women, CETP TaqIB, hepatic lipase, lipoprotein lipase, and apoCIII genotypes were tested against NMR-measured lipoprotein particle size distribution. Genotype effects were consistent across ethnicity but seen primarily in women: compared with CETP B1-allele carriers, B2B2 women had 16.4% higher HDL-cholesterol (P=0.001), 21.9% more large HDL particles (P=0.001), and larger mean HDL (2.3%, P=0.01) and LDL (1.3%, P=0.02) particle size. LPL 447X carriers had 21.0% lower VLDL-triglyceride (P=0.02), while apoCIII showed a male-specific effect (71.4% higher VLDL-TG in -455C carriers, P=0.0001), and hepatic lipase genotype showed no significant effects. The data confirm CETP, LPL, and apoCIII genetic variants shape the relationship among VLDL, LDL, and HDL particles.
Original abstract
Background And Aim: The effect of genetic variation on plasma lipoproteins and their subfraction distribution was examined.
Methods And Results: Forty Hispanic men and 223 women and 42 non-Hispanic white men and 53 women participated in the study. Genotypes for cholesteryl ester transfer protein (CETP TaqIB), hepatic lipase (LIPC -480 C > T), lipoprotein lipase (LPL S447X), and apolipoprotein CIII (APOC3--455T > C) were determined by polymerase chain reaction. Lipoprotein particle size distribution was determined by nuclear magnetic resonance. For all but APOC3, genotype effects were homogeneous in the ethnic/racial groups and men and women. Effects were seen primarily in the women. Compared to women carriers of the common CETP B1 allele, B2B2 women had significantly higher plasma levels of high-density lipoprotein cholesterol (HDL-C) (16.4.0%, p = 0.001), reflected in the level of larger HDL particles (21.9%, p = 0.001), and larger mean particle size of HDL (2.3%, p = 0.01) and low-density lipoproteins (LDL) (1.3%, p = 0.02). Compared to LPL 447S homozygous women carriers of the LPL 447X allele had significantly lower levels of very-low-density lipoprotein-triglyceride (VLDL-TG) (21.0%, p = 0.02). For APOC3, there was significant gender:genotype interaction with the genotype differences seen only in the men. Compared to men homozygous for the -455T allele, carriers of -455C had higher levels of VLDL-TG (71.4%, p = 0.0001), reflected in a larger mean VLDL particle size (13.7%, p = 0.009). LIPC genotype was not associated with significant effects on any of these traits.
Conclusion: These data confirm the role of genetic variants of CETP, LPL and APOC3 in determining the relationship between VLDL, LDL and HDL particles.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.