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

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.To test the association between two coding polymorphisms (c.29AC (Glu10Ala) and c.188GA (Cys63Tyr)) in PCTP gene and the LDL-PPD.LDL-PPD was measured by non-denaturating 2-16% polyacrylamide gradient gel electrophoresis on 623 QFS subjects.After adjustment for age and sex, carriers of the c.29C allele showed larger LDL-PPD than A/A homozygotes (p0.05). These results remained significant when LDL-PPD was further adjusted for the effects of BMI and triglyceride levels (p0.04). We also observed a three-fold lower risk of having the small (LDL-PPD256A), 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)).PCTP gene variants are associated with LDL-PPD.