No association of two functional polymorphisms in human ALOX15 with myocardial infarction.
The 12/15-lipoxygenase plays a janus-role in inflammation with pro-inflammatory and anti-inflammatory effects in cell systems and even opposite effects on atherosclerosis in two different animal species. Screening of the human 15-lipoxygenase (ALOX15) gene detected a polymorphic C to T substitution at position c.-292, which led to three times higher ALOX15 activity in macrophages and showed a trend to be atheroprotective in a small case-control study for coronary artery disease (CAD). A second polymorphism at position c.1693C>T leading to an T560M exchange and an inactive enzyme was recently associated with increased CAD. We now investigated whether these polymorphisms or a certain haplotype of ALOX15 are associated with myocardial infarction (MI) in a case-control subset from the population-based MONIKA/KORA cohort S3. Six polymorphisms in ALOX15 were analyzed in 2629 participants to cover all major haplotypes with a frequency higher than 1% in the Caucasian population. None of the polymorphism was associated with MI but a rare ALOX15 haplotype showed a significant protective effect on the risk for MI (p=0.03). However, none of the polymorphisms or haplotypes was associated with CRP levels. These data suggest that ALOX15 may play a less prominent role during later stages of atherosclerosis involving atherothrombotic mechanisms than eventually during early plaque development.
Hersberger
Martin
M
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich and Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland. martin.hersberger@kispi.uzh.ch
Müller
Martina
M
Marti-Jaun
Jacqueline
J
Heid
Iris M
IM
Coassin
Stefan
S
Young
Thomas F
TF
Waechter
Vanessa
V
Hengstenberg
Christian
C
Meisinger
Christine
C
Peters
Annette
A
König
Wolfgang
W
Holmer
Stephan
S
Schunkert
Heribert
H
Klopp
Norman
N
Kronenberg
Florian
F
Illig
Thomas
T
D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000378:metabolism
D002097:C-Reactive Protein; C515716:ALOX15 protein, human; D001093:Arachidonate 15-Lipoxygenase