title: A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma.
abstract: Cysteinyl-leukotrienes are important pro-inflammatory mediators in bronchial asthma (BA) and are derived from arachidonic acid by the action of 5-lipoxygenase. We identified a novel polymorphism, c.760 G>A (E254K), in exon 6 of the 5-lipoxygenase gene (5-LO). This substitution was detected in 11 out of 180 patients with BA, but not in any of the 150 non-allergic subjects. The frequency of c.760 G>A showed a significant difference between BA and non-allergic subjects (P=0.0007). The c.760 G>A polymorphism existed at the surface edge of the C-terminal catalytic domain, and the E-to-K substitution changed the charge of the side chain from negative to positive. Thus, our results suggest that E254K in the 5-LO might be associated with BA.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan.
authors.forename: Chunying
authors.initials: C
authors.lastname: Bai
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsui
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Kaori
authors.initials: K
authors.lastname: Kimata
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kasahara
authors.forename: Hideo
authors.initials: H
authors.lastname: Kaneko
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001249:Asthma / Q000201:enzymology* / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D015759:Ionomycin; D007975:Leukotriene B4 / Q000652:urine; D017999:Leukotriene E4 / Q000652:urine; D008239:Lysine / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: D012333:RNA, Messenger; D007975:Leukotriene B4; D018698:Glutamic Acid; D015759:Ionomycin; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; D008239:Lysine