Influences of the phosphatidylcholine transfer protein gene variants on the LDL peak particle size.
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.


OBJECTIVE
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 <256A), 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)).


CONCLUSIONS
PCTP gene variants are associated with LDL-PPD.
Dolley
G
G
CRML, CHUL Research Centre, 2705 Boul. Laurier, Ste-Foy, Canada.
Berthier
M T
MT
Lamarche
B
B
Després
J P
JP
Bouchard
C
C
Pérusse
L
L
Vohl
M C
MC
D015331:Cohort Studies; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D049294:Phospholipid Transfer Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci; D011792:Quebec
D008077:Lipoproteins, LDL; D049294:Phospholipid Transfer Proteins