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. 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 <256Å), 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.