A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma.
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.
Bai
Chunying
C
Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan.
Matsui
Eiko
E
Ohnishi
Hidenori
H
Kimata
Kaori
K
Kasahara
Kimiko
K
Kaneko
Hideo
H
Kato
Zenichiro
Z
Fukao
Toshiyuki
T
Kondo
Naomi
N
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
D012333:RNA, Messenger; D007975:Leukotriene B4; D018698:Glutamic Acid; D015759:Ionomycin; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; D008239:Lysine