Phosphoinositide cycle gene polymorphisms affect the plasma lipid profile in the Quebec Family Study

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 QTL for LDL-peak particle size (LDL-PPD) on the 17q21 region. Three positional candidates were identified in this region according to their implication in the phosphoinositide (PI) cycle: the myotubularin-related protein 4 (MTMR4), the phospholipase C, delta 3 (PLCD3), and the diacylglycerol kinase E (DGKE) genes. Objectives. To test the association between MTMR4, PLCD3, and DGKE gene polymorphisms, LDL-PPD and plasma lipid parameters. Methods. Analyses were performed on 680 subjects of QFS. LDL-PPD was measured by gradient gel electrophoresis on non-denaturating 2–16% polyacrylamide gradient gels. Direct sequencing was performed to identify genetic variations within these genes. Results. The c.-754G>C, c.183G>A, and c.579C>A DGKE SNPs were significantly associated with higher plasma triglyceride levels (p =0.029, p =0.008, p =0.001, respectively). The c.508C>G and c.890T>G MTMR4 polymorphisms were associated with plasma total-cholesterol concentrations (p =0.02, p =0.02, respectively), while no association was observed with PLCD3 gene polymorphisms. Conclusion. The c.579C>A DGKE gene polymorphism is associated with plasma triglyceride levels, while MTMR4 SNPs seem to predict variations in plasma cholesterol levels.