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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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.
