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Association of polymorphisms in the ALOX15B gene with coronary artery disease

Sophia J A Wuest1, Thomas Horn2, Jacqueline Marti-Jaun1

  • 1Division of Clinical Chemistry and Biochemistry, Children's Research Center, University Children's Hospital Zurich and Center for Integrative Human Physiology, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.

Clinical Biochemistry
|December 31, 2013
PubMed

Insights

Genetic variations in the ALOX15B gene are linked to coronary artery disease (CAD). Specific ALOX15B polymorphisms may influence CAD risk, but further research is needed to confirm these findings.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Biology
  • Biochemistry

Background:

  • Atherosclerosis, a key factor in cardiovascular diseases, involves lipid retention and inflammation.
  • 12/15-lipoxygenases play a role in inflammation and have been implicated in atherosclerosis.
  • While ALOX15 has a known role, the function of ALOX15B in human atherosclerosis remains unclear.

Purpose of the Study:

  • To investigate the association between ALOX15B gene polymorphisms and coronary artery disease (CAD).
  • To analyze the enzymatic activity and kinetics of identified ALOX15B variants.

Main Methods:

  • Screening of the ALOX15B gene for polymorphisms and association study with CAD in a case-control cohort (n=496).
  • In vitro measurement of enzyme activity and Michaelis-Menten kinetics for non-synonymous ALOX15B variants (p.Arg486His, p.Gln656Arg, p.Ile676Val).

Main Results:

  • Specific linked polymorphisms in ALOX15B (c.1458-38G>C, c.1579+71C>T, c.1656G>A) were associated with CAD (OR: 0.51, p=0.03).
  • The enzymatic activity and kinetics of the non-synonymous ALOX15B variants were comparable to the wild-type enzyme.

Conclusions:

  • The ALOX15B gene may be associated with coronary artery disease.
  • Larger studies are required to validate the association of these polymorphisms with CAD.
  • No frequent non-synonymous ALOX15B polymorphisms significantly altering enzyme activity were identified in Europeans.
Abstract

Keywords:
ALOX15BAtherosclerosisCoronary artery diseaseEpidermis-type 15-lipoxygenase 2Polymorphisms

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