Geiger Emanuel V, Doehring Alexandra, Kirchhof Anja, Lötsch Jörn
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University, Theodor Stern Kai 7, D-60590 Frankfurt am Main, Germany.
Prostaglandins Leukot Essent Fatty Acids. 2009 May-Jun;80(5-6):255-62. doi: 10.1016/j.plefa.2009.04.001. Epub 2009 May 14.
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.
5-脂氧合酶（ALOX5）基因的变异是白三烯起关键作用的疾病个体间差异的一线候选病因，例如炎症和免疫疾病、动脉粥样硬化、哮喘或急性呼吸窘迫综合征（ARDS）。我们开发并验证了用于单核苷酸多态性的焦磷酸测序筛选分析方法（dbSNP-ID：rs4986832、rs4987105、rs2115819、rs3740107、rs1565096、rs2291427、rs10571382、rs2242334、rs2229136、rs3802548），以及用于ALOX5 Sp1/Egr1启动子串联重复多态性的毛细管电泳分析方法。这一选择涵盖了整个ALOX5基因范围，并包括所有已报道具有功能关联的变异。对187名健康无亲缘关系的白种人的DNA进行基因结构分析，发现了两个单倍型模块，一个在启动子区，另一个从内含子6中的rs3740107G>A跨越六个单核苷酸多态性到外显子13中的rs2229136A>G。五重复基因型是最常见的Sp1/Egr1启动子串联重复变异（等位基因频率为84%）。这些分析方法和分析为未来评估白三烯生成的基因调控提供了坚实的基础。
