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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

Editorial Board Member: Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

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The c.–292C>T promoter polymorphism increases reticulocyte-type 15-lipoxygenase-1 activity and could be atheroprotective

Jonas Wittwer1 / Mathias Bayer2 / Armin Mosandl3 / Jörg Muntwyler4 / Martin Hersberger5

1Institute of Clinical Chemistry, Center for Integrative Human Physiology, University Hospital Zurich, Zurich, Switzerland

2Department of Food Chemistry, J.W. Goethe-University, Biocenter, Frankfurt am Main, Germany

3Department of Food Chemistry, J.W. Goethe-University, Biocenter, Frankfurt am Main, Germany

4Cardiovascular Center Division of Cardiology, University Hospital Zurich, Zurich, Switzerland

5Institute of Clinical Chemistry, Center for Integrative Human Physiology, University Hospital Zurich, Zurich, Switzerland

Corresponding author: Martin Hersberger, Institute of Clinical Chemistry, University Hospital Zurich, Raemistraβe 100, 8091 Zurich, Switzerland Phone: +41-44-2553473, Fax: +41-44-2554590,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 45, Issue 4, Pages 487–492, ISSN (Online) 14346621, ISSN (Print) 14374331, DOI: 10.1515/CCLM.2007.103, April 2007

Publication History

Received:
2006-10-13
Accepted:
2007-01-04
Published Online:
2007-04-17

Abstract

Background: Reticulocyte-type 15-lipoxygenase-1 (ALOX15) has anti-inflammatory and inflammatory effects and is implicated in the development of asthma, arthritis and atherosclerosis. Previously, we screened the human ALOX15 gene for variations because genetic variability in ALOX15 might influence these diseases. We found a C>T substitution at position c.–292 in the ALOX15 promoter that created a novel binding site for the transcription factor SPI1 and increased ALOX15 mRNA levels in monocytes from c.–292CT heterozygous volunteers.

Methods: To test whether the higher mRNA levels led to higher ALOX15 activity, we performed an activity assay and measured the arachidonic acid metabolite 15(S)-hydroxy-eicosatetraenoic acid [15(S)-HETE] by HPLC analysis. To test whether this polymorphism was associated with coronary artery disease (CAD), we investigated its association in a case-control study involving 498 Caucasians.

Results: The c.–292C>T polymorphism was associated with higher enzyme activity in heterozygous carriers. Intriguingly, this polymorphism also showed a tendency to be protective against atherosclerosis.

Conclusions: These results suggest that increased ALOX15 activity may attenuate inflammation, which could be caused by an increase in 15(S)-HETE and eventually by its metabolites, the lipoxins.

Clin Chem Lab Med 2007;45:487–92.

Keywords: inflammation; lipoxin; 15-lipoxygenase (15-LOX); polymorphism; PU.1; reticulocyte-type 15-lipoxygenase-1 (ALOX15); SFPI1; SPI1; transcription factor

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