出版社：American Society for Biochemistry and Molecular Biology
摘要：Phospholipid transfer protein (PLTP) participates in key processesin lipoprotein metabolism, including interparticle phospholipidtransfer, remodeling of HDL, cholesterol and phospholipid effluxfrom peripheral tissues, and the production of hepatic VLDL.The impact of PLTP on reverse cholesterol transport suggeststhat the gene may harbor sequence anomalies that contributeto disorders of HDL metabolism. The human PLTP gene was screenedfor sequence anomalies by DNA melting analysis in 276 subjectswith hypoalphalipoproteinemia (HA) and 364 controls. The associationwith plasma lipid parameters was evaluated. We discovered 18sequence variations, including four missense mutations and anovel polymorphism (c.-34G>C). In healthy controls, the c.-34G>Cminor allele was associated with higher high density lipoprotein-cholesterol(HDL-C) and was depleted in subjects with HA. Linear regressionmodels predict that possession of the rare allele decreasesplasma triglyceride (TG) and TG/HDL-C and increases HDL-C independentof TG. Decreased PLTP activity was observed in one (p.R235W)of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations inan in vitro activity assay. These findings indicate that PLTPgene variation is an important determinant of plasma lipoproteinsand affects disorders of HDL metabolism.Supplementary key words dyslipidemia • genetic polymorphism • atherosclerosis • cardiovascular diseases • phospholipid transfer protein
