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.
OBJECTIVE
The effect of genetic variation on plasma lipoproteins and their subfraction distribution was examined.


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.


CONCLUSIONS
These data confirm the role of genetic variants of CETP, LPL and APOC3 in determining the relationship between VLDL, LDL and HDL particles.
Humphries
S E
SE
Division of Cardiovascular Genetics, Dept. of Medicine, UCL Medical School, Rayne Institute, University Street, London WC1E 6JJ, UK. rmhaseh@ucl.ac.uk
Berglund
L
L
Isasi
C R
CR
Otvos
J D
JD
Kaluski
D
D
Deckelbaum
R J
RJ
Shea
S
S
Talmud
P J
PJ
D000328:Adult; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006023:Glycoproteins; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000235:genetics*; D010316:Particle Size; D016133:Polymerase Chain Reaction; D012737:Sex Factors; D044465:White People / Q000235:genetics*
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D015415:Biomarkers; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D008055:Lipids; D002784:Cholesterol; D008049:Lipase; D008071:Lipoprotein Lipase