Exp Mol Med.  2015 Apr;47(4):e157. 10.1038/emm.2015.10.

Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma

• Kim SH
• Bae SJ
• Palikhe S
• Ye YM
• Park HS

• KMID: 2070276
• DOI: http://doi.org/10.1038/emm.2015.10

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.

MeSH Terms

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
Immunoglobulin E
Immunoglobulin G
Isocyanates
Mannose-Binding Lectin