Apolipoprotein L-I is positively associated with hyperglycemia and plasma triglycerides in CAD patients with low HDL

Timothy S.E Albert,Philippe N Duchateau,Samir S Deeb,Clive R Pullinger,Min H Cho,David C Heilbron,Mary J Malloy,John P Kane,B Greg Brown

doi:10.1194/jlr.m400304-jlr200

Timothy S.E Albert, Philippe N Duchateau + Show 7 more

Open Access

https://doi.org/10.1194/jlr.m400304-jlr200

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Abstract

Apolipoprotein L-I (apoL-I) is present on a subset of HDL particles and is positively correlated with plasma triglycerides (TGs). We measured plasma apoL-I levels in coronary artery disease (CAD) subjects with low HDL who were enrolled in an angiographic CAD prevention trial. At baseline, apoL-I levels (n = 136; range, 2.2-64.1 mug/ml) were right skewed with a large degree of variability. Multivariate analysis for biological determinants of apoL-I revealed that the log of VLDL-TG (+0.17; P < 0.05) and hyperglycemia (HG; +0.26; P < 0.005) independently predicted apoL-I level. Hyperglycemic patients (n = 24) had mean apoL-I levels >50% higher than normoglycemic subjects (n = 112; 13.2 vs. 8.3 mug/ml, respectively; P < 0.001). No relationship between apoL-I level and change in CAD was found (r = 0.06, P = 0.49). Simvastatin-niacin therapy did not alter apoL-I levels (n = 34; P = 0.27), whereas antioxidant vitamins alone increased apoL-I by >50% (n = 36; P < 0.01). Genotyping of a known apoL-I polymorphism (Lys166Glu) did not independently account for any of the variability in apoL-I levels. In conclusion, we found TG and HG to be the strongest predictors of apoL-I within a dyslipidemic CAD population. These data provide further characterization of the novel HDL-associated apoL-I.

Highlights

Supplementary key words diabetes mellitus coronary artery disease lipids antioxidant vitamins statins niacin high density lipoprotein
ApoL-I, the original protein described in this family, is a 42 kDa protein that is found in the plasma mainly associated with large-diameter HDL particles [1]
ApoL-I is right skewed with a bimodal appearance Figure 1 shows the right skewed, nonnormal distribution of Apolipoprotein L-I (apoL-I) in the HDL Atherosclerosis Treatment Study (HATS) population

Summary

Introduction

Our group and another have identified a cluster of apoL genes on chromosome 22 that encode up to six apoL proteins (apoL-I to apoL-VI) [2, 3] These genes have putative sterol response elements in their promoters, and sequence analysis has revealed conserved amphipathic helices, suggesting that they may be involved in lipid metabolism [2, 3]. HATS was a coronary artery disease (CAD) prevention trial that enrolled patients with documented CAD who, as a group, had dyslipidemia characterized by low plasma HDL-cholesterol (HDL-C) concentrations and mildly increased TGs. Our goals were to determine what metabolic factor(s) were most closely associated with apoL-I plasma levels, to determine the distribution of apoL-I in a dyslipidemic population with CAD, and to determine if apoL-I was associated with the progression or regression of CAD and/or affected by drug therapy.

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