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.

Keywords: coronary artery disease; paraoxonase 1; phospholipid transfer protein.

Fig. 1.

Correlation between PLTPa measurements from the gold-standard radiometric liposome assay used in the current study and the widely used commercial fluorometric liposome assay. The black line represents the correlation coefficient from a classical linear regression model between the two PLTPa assays.

Fig. 2.

OR association with CAAD status of PLTPa and predictors from multivariate logistic regression (n = 1,056). *0.05 > P > 0.001. **P < 0.001. See supplementary Table 4 for full regression model coefficients.