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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.

SUBMITTER: Kim DS

PROVIDER: S-EPMC4479339 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity.

Kim Daniel Seung DS Burt Amber A AA Ranchalis Jane E JE Vuletic Simona S Vaisar Tomas T Li Wan-Fen WF Rosenthal Elisabeth A EA Dong Weijiang W Eintracht Jason F JF Motulsky Arno G AG Brunzell John D JD Albers John J JJ Furlong Clement E CE Jarvik Gail P GP

Journal of lipid research 20150525 7

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 particip ...[more]

PMID: 26009633

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Project description:The importance of high-density lipoprotein (HDL) particle components to reproduction is increasingly recognized, including the constituent paraoxonase 1 (PON1). However, the reliability characteristics of PON1 enzymes in ovarian follicular fluid (FF) as biomarkers for clinical and epidemiologic studies have not been described. Therefore, we characterized PON1 enzymes in FF and serum and assessed the impact of the PON1 Q192R polymorphism on associations between enzyme activities in two compartments. We also evaluated associations between HDL particle size and enzyme activities. We collected FF and serum from 171 women undergoing in vitro fertilization. PON1 activities were measured as paraoxonase and arylesterase activities, and HDL particle size was determined by 1H NMR spectrometry. Reliability indices for PON1 activities were characterized and we evaluated HDL particle sizes as predictors of PON1 enzyme activities. We found that PON1 enzyme activities were correlated between compartments, but higher in serum than in FF. For FF, the index of individuality (II) was low and the coefficient of variation (CV%) was high for paraoxonase activity overall (0.12 and 11.51%, respectively). However, IIs increased (0.33-1.30) and CV%s decreased (5.58%-8.52%) when stratified by PON1 Q192R phenotype. The intraclass correlation coefficient (ICC) for FF paraoxonase activity was high overall (0.89) but decreased when stratified by PON1 Q192R phenotype (0.43-0.75). We found similar, although more modest, patterns for FF arylesterase activity. For enzyme activities in serum, ICCs were close to 1.00 across all phenotypes. Additionally, different HDL particle sizes predicted PON1 enzyme activities according to PON1 Q192R phenotype. Overall, stratification by PON1 Q192R phenotype improved the reliability characteristics of FF PON1 enzymes as biomarkers for use in clinical investigations but diminished usefulness for epidemiologic studies. Thus, we recommend stratification by PON1 Q192R phenotype for clinical but not epidemiologic investigations, when employing FF PON1 enzyme activity biomarkers.

Dataset Information

PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity.

Publications

PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity.

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