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.
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.
Authors: Marguerite R Irvin; Amy I Lynch; Edmond K Kabagambe; Hemant K Tiwari; Joshua I Barzilay; John H Eckfeldt; Eric Boerwinkle; Barry R Davis; Charles E Ford; Donna K Arnett Journal: J Hypertens Date: 2010-10 Impact factor: 4.844
Authors: Vicky Brocklebank; Gurinder Kumar; Alexander J Howie; Jayanthi Chandar; David V Milford; Janet Craze; Jonathan Evans; Eric Finlay; Michael Freundlich; Daniel P Gale; Carol Inward; Martin Mraz; Caroline Jones; William Wong; Stephen D Marks; John Connolly; Bronte M Corner; Kate Smith-Jackson; Patrick R Walsh; Kevin J Marchbank; Claire L Harris; Valerie Wilson; Edwin K S Wong; Michal Malina; Sally Johnson; Neil S Sheerin; David Kavanagh Journal: Kidney Int Date: 2020-02-28 Impact factor: 10.612