title: Functional variants of the human 5-lipoxygenase gene and their genetic diagnosis.
abstract: Variants in the 5-lipoxygenase (ALOX5) gene are first-line candidate causes for interindividual differences in diseases where leukotrienes play a key role, e.g., inflammatory and immune diseases, atherosclerosis, asthma or the acute respiratory distress syndrome (ARDS). We developed and validated Pyrosequencing screening assays for single nucleotide polymorphism (dbSNP-IDs rs4986832, rs4987105, rs2115819, rs3740107, rs1565096, rs2291427, rs10571382, rs2242334, rs2229136, rs3802548), and a capillary electrophoresis assay for the ALOX5 Sp1/Egr1 promoter tandem repeat polymorphism. This selection spans the whole ALOX5 gene range and includes all variants with reported functional associations. A gene structure analysis in DNAs from 187 healthy unrelated Caucasians revealed two haploblocks, one in the promoter and one spanning six SNPs from rs3740107G>A in intron 6 to rs2229136A>G in exon 13. The five-repeat genotype was the most frequent Sp1/Egr1 promoter tandem repeat variant (allelic frequency 84%). These assays and analyses provide a solid basis for future assessments of the genetic modulation of leukotriene production.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University, Theodor Stern Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Emanuel V
authors.initials: EV
authors.lastname: Geiger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Doehring
authors.forename: Anja
authors.initials: A
authors.lastname: Kirchhof
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase