title: PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity.
abstract: Recent studies have failed to demonstrate a causal cardioprotective effect of HDL cholesterol levels, shifting focus to the functional aspects of HDL. Phospholipid transfer protein (PLTP) is an HDL-associated protein involved in reverse cholesterol transport. This study sought to determine the genetic and nongenetic predictors of plasma PLTP activity (PLTPa), and separately, to determine whether PLTPa predicted carotid artery disease (CAAD). PLTPa was measured in 1,115 European ancestry participants from a case-control study of CAAD. A multivariate logistic regression model was used to elucidate the relationship between PLTPa and CAAD. Separately, a stepwise linear regression determined the nongenetic clinical and laboratory characteristics that best predicted PLTPa. A final stepwise regression considering both nongenetic and genetic variables identified the combination of covariates that explained maximal PLTPa variance. PLTPa was significantly associated with CAAD (7.90 × 10(-9)), with a 9% decrease in odds of CAAD per 1 unit increase in PLTPa (odds ratio = 0.91). Triglyceride levels (P = 0.0042), diabetes (P = 7.28 × 10(-5)), paraoxonase 1 (PON1) activity (P = 0.019), statin use (P = 0.026), PLTP SNP rs4810479 (P = 6.38 × 10(-7)), and PCIF1 SNP rs181914932 (P = 0.041) were all significantly associated with PLTPa. PLTPa is significantly inversely correlated with CAAD. Furthermore, we report a novel association between PLTPa and PON1 activity, a known predictor of CAAD.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
authors.forename: Daniel Seung
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Amber A
authors.initials: AA
authors.lastname: Burt
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Ranchalis
authors.affiliation: Northwest Lipid Metabolism and Diabetes Research Laboratories, Seattle, WA Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Simona
authors.initials: S
authors.lastname: Vuletic
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaisar
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Wan-Fen
authors.initials: WF
authors.lastname: Li
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Rosenthal
authors.affiliation: Northwest Lipid Metabolism and Diabetes Research Laboratories, Seattle, WA Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Human Anatomy and Histology and Embryology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, People's Republic of China.
authors.forename: Weijiang
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of General Medicine, Virginia Mason Medical Center, Seattle, WA.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Eintracht
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA.
authors.forename: Arno G
authors.initials: AG
authors.lastname: Motulsky
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: John D
authors.initials: JD
authors.lastname: Brunzell
authors.affiliation: Northwest Lipid Metabolism and Diabetes Research Laboratories, Seattle, WA Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Albers
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA.
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
mesh_terms: D000368:Aged; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D008055:Lipids; D049294:Phospholipid Transfer Proteins; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: coronary artery disease; paraoxonase 1; phospholipid transfer protein