ALOX5


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ALOX5

A gene on chromosome 10q11.2 that encodes a member of the lipoxygenase (LOX) family of non-heme iron dioxygenases, which are involved in the production and metabolism of fatty acid hydroperoxidases.

Molecular pathology
Mutations in the ALOX5 promoter region lead to a reduced response to antileukotriene drugs used for asthma, and may also be linked to atherosclerosis and several cancers.
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The omega 3s inhibit the activity of ALOX5, an enzyme that exacerbates lung inflammation and causes asthma.
ALOX5 is an enzyme present in many inflammatory cells that makes inflammatory proteins called leukotrienes.
However, of more than 100 genes of potential interest, ADRB2 and ALOX5 are perhaps the most clinically relevant.
Polymorphisms in ALOX5 and also in 5-lipoxygenase-activating-protein (FLAP) are associated with the excessive production of leukotrienes (Koshino et al.
2007) found that a subset of asthmatics with ALOX5 polymorphisms were predisposed to having higher cysteinyl-leukotriene (cys-LT) concentrations, and they constituted an asthma phenotype more likely to respond to a leukotriene-inhibiting drug such as montelukast.
Components in fish oil (omega-3 fatty acids, composed of EPA and DHA) suppress the production of arachidonic acid-derived leukotrienes via the ALOX5 pathway.
EPA-enriched fish oils may competitively inhibit the production of LTC4 by competing with arachidonic acid as a substrate for ALOX5 (fig.
2: Specifically enriched fish oils compete with arachidonic acid for the ALOX5 enzyme, potentially decreasing the production of inflammatory leukotrienes.
The hypothesis is that fish oil supplementation can impede the production of inflammatory leukotrienes in asthmatics with SNPs in the promoter of ALOX5.
We have performed genotyping of the ALOX5 gene in a full cohort of 35 subjects, 22 of whom are female.
TABLE 1: Prevalence of ALOX5 genotypes in asthma cohort (n = 35) [Table omitted]
TABLE 2: Classification of high-risk and control ALOX5 genotypes [Table omitted]