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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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CiteScore 2018: 2.44

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Volume 47, Issue 4


Minimizing the effects of multicollinearity in the polynomial regression of age relationships and sex differences in serum levels of pregnenolone sulfate in healthy subjects

Milan Meloun
  • Department of Analytical Chemistry, Faculty of Chemical Technology, Pardubice University, Pardubice, Czech Republic
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Martin Hill / Helena Včeláková-Havlíková
Published Online: 2009-03-12 | DOI: https://doi.org/10.1515/CCLM.2009.104


Background: Pregnenolone sulfate (PregS) is known as a steroid conjugate positively modulating N-methyl-D-aspartate receptors on neuronal membranes. These receptors are responsible for permeability of calcium channels and activation of neuronal function. Neuroactivating effect of PregS is also exerted via non-competitive negative modulation of GABAA receptors regulating the chloride influx. Recently, a penetrability of blood-brain barrier for PregS was found in rat, but some experiments in agreement with this finding were reported even earlier. It is known that circulating levels of PregS in human are relatively high depending primarily on age and adrenal activity.

Methods: Concerning the neuromodulating effect of PregS, we recently evaluated age relationships of PregS in both sexes using polynomial regression models known to bring about the problems of multicollinearity, i.e., strong correlations among independent variables. Several criteria for the selection of suitable bias are demonstrated. Biased estimators based on the generalized principal component regression (GPCR) method avoiding multicollinearity problems are described.

Results: Significant differences were found between men and women in the course of the age dependence of PregS. In women, a significant maximum was found around the 30th year followed by a rapid decline, while the maximum in men was achieved almost 10 years earlier and changes were minor up to the 60th year. The investigation of gender differences and age dependencies in PregS could be of interest given its well-known neurostimulating effect, relatively high serum concentration, and the probable partial permeability of the blood-brain barrier for the steroid conjugate.

Conclusions: GPCR in combination with the MEP (mean quadric error of prediction) criterion is extremely useful and appealing for constructing biased models. It can also be used for achieving such estimates with regard to keeping the model course corresponding to the data trend, especially in polynomial type regression models.

Clin Chem Lab Med 2009;47:464–70.

Keywords: age relationship of pregnenolone sulfate; multicollinearity; principal component regression; steroids

About the article

Corresponding author: Prof. RNDr. Milan Meloun, DrSc, Department of Analytical Chemistry, University Pardubice, 532 10 Pardubice, Czech Republic Phone: +42-46-6037026, Fax: +42-46-6037068,

Received: 2008-11-28

Accepted: 2009-01-09

Published Online: 2009-03-12

Published in Print: 2009-04-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 47, Issue 4, Pages 464–470, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2009.104.

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