title: Association of polymorphisms in the ALOX15B gene with coronary artery disease.
abstract: BACKGROUND
  Atherosclerosis is a multifactorial disease and the underlying cause of coronary artery disease (CAD), myocardial infarction and stroke. Two main features are involved in the progression of atherosclerosis, lipid retention and inflammation. 12/15-lipoxygenases are involved in inflammation and have been implicated in atherosclerosis. Genetic association studies of the 15-lipoxygenase 1 (ALOX15) in humans revealed a neutral to atheroprotective role of the enzyme. Recently the epidermis-type 15-lipoxygenase 2 (ALOX15B) has been identified in human atherosclerotic plaques but its role in human atherosclerosis is still unclear.
  
  
  METHODS
  We screened the ALOX15B gene for polymorphisms and investigated the association of 18 detected polymorphisms with angiographically documented CAD in a case-control study (n=496). In addition, we measured in vitro the enzyme activity and Michaelis-Menten kinetics of the detected non-synonymous polymorphic variants p.Arg486His (c.1457G>A), p.Gln656Arg (c.1967A>G) and p.Ile676Val (c.2026A>G).
  
  
  RESULTS
  We found that the linked polymorphisms at position c.1458-38G>C, c.1579+71C>T and c.1656G>A are associated with CAD (OR: 0.51 (0.27-0.94), p-value: 0.03). In addition, we show that the activity and the kinetics of the three non-synonymous ALOX15B enzyme variants (p.Arg486His, p.Gln656Arg and p.Ile676Val) are similar to the wild-type enzyme.
  
  
  CONCLUSIONS
  Our data indicate that the ALOX15B gene may be associated with coronary artery disease. However, larger studies would be necessary to confirm the association of these polymorphisms with CAD. In contrast, our study did not find frequent non-synonymous polymorphisms in ALOX15B altering enzyme activity in Europeans.
authors.affiliation: Division 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.
authors.forename: Sophia J A
authors.initials: SJ
authors.lastname: Wuest
authors.affiliation: Institute of Biochemistry, University Medicine Berlin - Charité, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Horn
authors.affiliation: Division 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.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marti-Jaun
authors.affiliation: Institute of Biochemistry, University Medicine Berlin - Charité, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kühn
authors.affiliation: Division 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; Institute of Physiology and Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address: martin.hersberger@kispi.uzh.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
mesh_terms: D000368:Aged; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007700:Kinetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013816:Thermodynamics
chemical_list: C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase
keywords: ALOX15B; Atherosclerosis; Coronary artery disease; Epidermis-type 15-lipoxygenase 2; Polymorphisms