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.