title: Genetic variation in phospholipid transfer protein modulates lipoprotein profiles in hyperalphalipoproteinemia.
abstract: We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.
authors.affiliation: Department of Physiological Nursing, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Engler
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
authors.forename: Yanina
authors.initials: Y
authors.lastname: Natanzon
authors.forename: Medha V
authors.initials: MV
authors.lastname: Kulkarni
authors.forename: James
authors.initials: J
authors.lastname: Song
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Jaarko
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: John
authors.initials: J
authors.lastname: Kane
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells; D016022:Case-Control Studies; D002522:Chlorocebus aethiops; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000235:genetics*; D012189:Retrospective Studies; D014162:Transfection
chemical_list: D008074:Lipoproteins; D008075:Lipoproteins, HDL; D049294:Phospholipid Transfer Proteins