Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma.
- Author:
Seung Hyun KIM
1
;
Su Jin BAE
;
Sailesh PALIKHE
;
Young Min YE
;
Hae Sim PARK
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: Adult; Alleles; Asthma, Occupational/diagnosis/*etiology; Cell Line; Female; Forced Expiratory Volume; Gene Frequency; Genotype; Haplotypes; Humans; Immunoglobulin E/immunology; Immunoglobulin G/immunology; Isocyanates/*adverse effects/immunology; Male; Mannose-Binding Lectin/blood/*genetics; Middle Aged; *Polymorphism, Genetic; Polymorphism, Single Nucleotide; Protein Binding; Transcriptional Activation; Young Adult
- From:Experimental & Molecular Medicine 2015;47(4):e157-
- CountryRepublic of Korea
- Language:English
- 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.
