title: Genetic variation of PLTP modulates lipoprotein profiles in hypoalphalipoproteinemia.
abstract: Phospholipid transfer protein (PLTP) participates in key processes in lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. The impact of PLTP on reverse cholesterol transport suggests that the gene may harbor sequence anomalies that contribute to disorders of HDL metabolism. The human PLTP gene was screened for sequence anomalies by DNA melting analysis in 276 subjects with hypoalphalipoproteinemia (HA) and 364 controls. The association with plasma lipid parameters was evaluated. We discovered 18 sequence variations, including four missense mutations and a novel polymorphism (c.-34G > C). In healthy controls, the c.-34G > C minor allele was associated with higher high density lipoprotein-cholesterol (HDL-C) and was depleted in subjects with HA. Linear regression models predict that possession of the rare allele decreases plasma triglyceride (TG) and TG/HDL-C and increases HDL-C independent of TG. Decreased PLTP activity was observed in one (p.R235W) of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations in an in vitro activity assay. These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism.
authors.affiliation: Department of Physiological Nursing, School of Nursing, University of California San Francisco, San Francisco, CA 94143, USA. bradley.aouizerat@nursing.ucsf.edu
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.forename: Mary B
authors.initials: MB
authors.lastname: Engler
authors.forename: Yanina
authors.initials: Y
authors.lastname: Natanzon
authors.forename: Medha
authors.initials: M
authors.lastname: Kulkarni
authors.forename: James
authors.initials: J
authors.lastname: Song
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Jarkko
authors.initials: J
authors.lastname: Huuskonen
authors.forename: Christopher
authors.initials: C
authors.lastname: Rivera
authors.forename: Annie
authors.initials: A
authors.lastname: Poon
authors.forename: Matt
authors.initials: M
authors.lastname: Bensley
authors.forename: Amy
authors.initials: A
authors.lastname: Sehnert
authors.forename: Christian
authors.initials: C
authors.lastname: Zellner
authors.forename: Mary
authors.initials: M
authors.lastname: Malloy
authors.forename: John
authors.initials: J
authors.lastname: Kane
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D049294:Phospholipid Transfer Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012189:Retrospective Studies; D013631:Tangier Disease / Q000097:blood / Q000235:genetics*
chemical_list: D008074:Lipoproteins; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins