Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma
Experimental & Molecular Medicine
; : e157-2015.
Article
in En
| WPRIM
| ID: wpr-147139
Responsible library:
WPRO
ABSTRACT
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 G>C, - 431A>C and - 225 G>C) 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 (P<0.001) 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.
Full text:
1
Index:
WPRIM
Main subject:
Polymorphism, Genetic
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Protein Binding
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Haplotypes
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Immunoglobulin E
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Immunoglobulin G
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Transcriptional Activation
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Cell Line
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Forced Expiratory Volume
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Isocyanates
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Polymorphism, Single Nucleotide
Limits:
Adult
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Female
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Humans
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Male
Language:
En
Journal:
Experimental & Molecular Medicine
Year:
2015
Type:
Article