title: Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma.
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.
authors: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors: Seung-Hyun
authors: SH
authors: Kim
authors: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors: Su-Jin
authors: SJ
authors: Bae
authors: 1] Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea [2] Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, South Korea.
authors: Sailesh
authors: S
authors: Palikhe
authors: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors: Young-Min
authors: YM
authors: Ye
authors: 1] Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea [2] Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, South Korea.
authors: Hae-Sim
authors: HS
authors: Park
mesh_terms: D000328:Adult; D000483:Alleles; D059366:Asthma, Occupational / Q000175:diagnosis / Q000209:etiology*; D002460:Cell Line; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D017953:Isocyanates / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D015533:Transcriptional Activation; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D017953:Isocyanates; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D007073:Immunoglobulin E