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Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea. Mannose-binding lectin (MBL) initiates the lectin complement activation pathway following oxidative stress and plays an important role in the regulation of inflammatory processes. To determine whether there is a genetic association between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic exposed controls (AECs) and 144 unexposed normal controls were enrolled in this study. Three polymorphisms (−554 G4C, − 431A4C and − 225 G4C) in the MBL2 promoter were genotyped, and serum MBL levels were determined by enzyme-linked immunosorbent assay. Functional variabilities in the promoter polymorphisms were analyzed by a luciferase reporter assay and electrophoretic mobility shift assay (EMSA). A significantly higher frequency of haplotype (ht) 2 [CAG] was noted in the DI-OA group compared with the AEC group (P=0.044). The patients with DI-OA carrying ht2 [CAG] had significantly lower PC20 methacholine levels (Po0.001) than the non-carriers. The serum MBL levels were significantly higher in the DI-exposed subjects (both the DI-OA patients and AECs) carrying ht1 [GAG] (P=0.028). Luciferase activity was significantly enhanced in ht1 [GAG] compared with ht2 [CAG] in human hepatocarcinoma cells (Hep3B) (P=0.002). The EMSA showed that a − 554G probe produced a specific shifted band compared with the − 554C probe. These findings suggest that decreased serum MBL levels due to polymorphisms of the MBL2 gene may increase susceptibility to the development of DI-OA in DI-exposed individuals.
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참고문헌 (24)
참고문헌 신청
Bae SJ / 2013 / Mannose-binding lectin 2gene polymorphisms affect serum mannose-binding lectin levels in adult asthmatics / Ann Allergy Asthma Immunol 111 : 71 ~ 73
Collard CD / 2000 / Complement activation after oxidative stress : role of the lectin complement pathway / Am J Pathol 156 : 1549 ~ 1556
Collard CD / 2001 / Endothelial oxidative stress activates the lectin complement pathway : role of cytokeratin 1 / Am J Pathol 159 : 1045 ~ 1054
Dozor AJ. / 2010 / The role of oxidative stress in the pathogenesis and treatment of asthma / Ann N Y Acad Sci 1203 : 133 ~ 137
Dworski R / 2001 / Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2-isoprostane, 15-F2t-IsoP (8-iso-PGF2alpha) / Clin Exp
Collard CD / 2000 / Complement activation after oxidative stress : role of the lectin complement pathway / Am J Pathol 156 : 1549 ~ 1556
Collard CD / 2001 / Endothelial oxidative stress activates the lectin complement pathway : role of cytokeratin 1 / Am J Pathol 159 : 1045 ~ 1054
Dozor AJ. / 2010 / The role of oxidative stress in the pathogenesis and treatment of asthma / Ann N Y Acad Sci 1203 : 133 ~ 137
Dworski R / 2001 / Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2-isoprostane, 15-F2t-IsoP (8-iso-PGF2alpha) / Clin Exp
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