Quantification of Lipoprotein Subclasses by Proton Nuclear Magnetic Resonance–Based Partial Least-Squares Regression Models

Author:

Petersen Martin1,Dyrby Marianne2,Toubro Søren1,Engelsen Søren Balling3,Nørgaard Lars3,Pedersen Henrik Toft4,Dyerberg Jørn1

Affiliation:

1. Institute of Human Nutrition, Centre for Advanced Food Studies, and

2. Umetrics AB, Malmö, Sweden

3. Centre for Advanced Food Studies, Department of Food Science, Quality and Technology, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark

4. Novo Nordisk A/S, Virology & Molecular Toxicology, Måløv, Denmark

Abstract

AbstractBackground: Cardiovascular disease risk can be estimated in part on the basis of the plasma lipoprotein profile. Analysis of lipoprotein subclasses improves the risk evaluation, but the traditional methods are very time-consuming. Novel, rapid, and productive methods are therefore needed.Methods: We obtained plasma samples from 103 fasting people and determined the plasma lipoprotein subclass profiles by an established ultracentrifugation-based method. Proton nuclear magnetic resonance (NMR) spectra were obtained from replicate samples on a 600 MHz NMR spectrometer. From the ultracentrifugation-based reference data and the NMR spectra, we developed partial least-squares (PLS) regression models to predict cholesterol and triglyceride (TG) concentrations in plasma as well as in VLDL, intermediate-density lipoprotein (IDL), LDL, 3 LDL fractions, HDL, and 3 HDL subclasses.Results: The correlation coefficients (r) between the plasma TG and cholesterol concentrations measured by the 2 methods were 0.98 and 0.91, respectively. For LDL- and HDL-cholesterol concentrations, r = 0.90 and 0.94, respectively. For cholesterol concentrations in the LDL-1, LDL-2, and LDL-3 fractions, r = 0.74, 0.78, and 0.69, respectively, and for HDL subclasses HDL2b, HDL2a, and HDL3, cholesterol concentrations were predicted with r = 0.92, 0.94, and 0.75, respectively. TG concentrations in VLDL, IDL, LDL, and HDL were predicted with correlations of 0.98, 0.85, 0.77, and 0.74, respectively. The cholesterol and TG concentrations in the main lipoprotein fractions and in LDL fractions and HDL subclasses predicted by the PLS models were 94%–100% of the concentrations obtained by ultracentrifugation.Conclusion: NMR-based PLS regression models are appropriate for use in research in which analyses of the plasma lipoprotein profile, including LDL and HDL subclasses, are required in large numbers of samples.

Publisher

Oxford University Press (OUP)

Subject

Biochemistry, medical,Clinical Biochemistry

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