Abstract
Background
The small, dense LDL phenotype is associated with an increased cardiovascular disease
risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study
(QFS) revealed a quantitative trait locus (QTL) affecting LDL peak particle size (LDL-PPD)
and density on the 17q21 region. This region contains the phosphatidylcholine transfer
protein gene (PCTP). In the liver, phosphatidylcholine transfer protein binds specifically
phosphatidylcholine suggesting a role for this protein in the formation of HDL and
possibly VLDL phospholipid membranes.
Objectives
To test the association between two coding polymorphisms (c.29A>C (Glu10Ala) and c.188G>A
(Cys63Tyr)) in PCTP gene and the LDL-PPD.
Methods
LDL-PPD was measured by non-denaturating 2–16% polyacrylamide gradient gel electrophoresis
on 623 QFS subjects.
Results
After adjustment for age and sex, carriers of the c.29C allele showed larger LDL-PPD
than A/A homozygotes (p < 0.05). These results remained significant when LDL-PPD was further adjusted for the
effects of BMI and triglyceride levels (p < 0.04). We also observed a three-fold lower risk of having the small (LDL-PPD <256 Å), dense LDL phenotype in subjects carrying the c.29C allele, when compared to A/A
homozygotes (OR = 0.35 (95% CI: 0.14–0.91; p = 0.03)).
Conclusion
PCTP gene variants are associated with LDL-PPD.
Abbreviations:
APOH (apolipoprotein H gene), CHD (coronary heart disease), GGE (gradient gel electrophoresis), HDL (high-density lipoprotein), HDL-C (high-density lipoprotein cholesterol), HDL2-C (high-density lipoprotein 2 cholesterol), HDL3-C (high-density lipoprotein 3 cholesterol), LDL (low-density lipoprotein), LDL-C (low-density lipoprotein cholesterol), LDL-PPD (low-density lipoprotein peak particle diameter), PCTP (phosphatidylcholine transfer protein gene), QFS (Quebec Family Study), QTL (quantitative trait locus), SNP (single nucleotide polymorphism), VLDL (very-low density lipoprotein)Keywords
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References
- Identification of multiple subclasses of plasma low density lipoproteins in normal humans.J Lipid Res. 1982; 23: 97-104
- Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.Circulation. 1997; 95: 69-75
- Dietary and genetic effects on low-density lipoprotein heterogeneity.Annu Rev Nutr. 2001; 21: 283-295
- Effects of the amount and intensity of exercise on plasma lipoproteins.N Engl J Med. 2002; 347: 1483-1492
- Genetics of LDL particle heterogeneity: from genetic epidemiology to DNA-based variations.J Lipid Res. 2004; 45: 1008-1026
- Heritability of LDL peak particle diameter in the Quebec Family Study.Genet Epidemiol. 2003; 25: 375-381
- Detection of a major gene effect for LDL peak particle diameter and association with apolipoprotein H gene haplotype.Atherosclerosis. 2005; 182: 231-239
- Genetics of LDL subclass phenotypes in women twins. concordance, heritability, and commingling analysis.Arterioscler Thromb. 1993; 13: 687-695
- Evidence for a major quantitative trait locus on chromosome 17q21 affecting low-density lipoprotein peak particle diameter.Circulation. 2003; 107: 2361-2368
- Structure of human phosphatidylcholine transfer protein in complex with its ligand.Nat Struct Biol. 2002; 9: 507-511
- Genetic epidemiology, association, and sib-pair linkage: results from the Québec Family Study.in: Bray G.A. Ryan D.H. Molecular and genetic aspects of obesity. Louisiana State University Press, Baton Rouge1996: 470-481
- Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease.Circulation. 2001; 104: 2295-2299
- Enzymatic determination of total serum cholesterol.Clin Chem. 1974; 20: 470-475
- Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide.Clin Chem. 1982; 28: 2077-2080
- On a rapid determination of the cholesterol bound to the serum alpha- and beta-lipoproteins.Clin Chim Acta. 1960; 5: 609
- Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies.Anal Biochem. 1966; 15: 45-52
- A new DNA sequence assembly program.Nucl Acids Res. 1995; 23: 4992-4999
- Low-density lipoprotein subclass patterns and risk of myocardial infarction.JAMA. 1988; 260: 1917-1921
- A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men.Can J Cardiol. 2001; 17: 859-865
- The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes.J Biol Chem. 1988; 263: 2998-3004
- Reduction in VLDL, but not HDL, in plasma of rats deficient in choline.Biochem Cell Biol. 1990; 68: 552-558
- Determinants of the selection of phosphatidylcholine molecular species for secretion into bile in the rat.Hepatology. 1998; 28: 631-637
- Phosphatidylcholine transfer protein promotes apolipoprotein A-I-mediated lipid efflux in chinese hamster ovary cells.J Biol Chem. 2002; 277: 6198-6206
- Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins.Am J Physiol Gastrointest Liver Physiol. 2005; 289: G1067-G1074
- Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia.J Lipid Res. 2003; 44: 2161-2168
- Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia.J Lipid Res. 2000; 41: 245-252
- Low-density lipoprotein particle size loci in familial combined hyperlipidemia: evidence for multiple loci from a genome scan.Arterioscler Thromb Vasc Biol. 2004; 24: 1942-1950
- A novel quantitative trait locus on chromosome 1 with pleiotropic effects on HDL-cholesterol and LDL particle size in hypertensive sibships.Am J Hypertens. 2005; 18: 1084-1090
Article Info
Publication History
Published online: January 31, 2007
Accepted:
January 2,
2007
Received in revised form:
December 21,
2006
Received:
November 27,
2006
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
