哮喘联盟

   摘要
   二异氰酸酯（DI）是韩国职业性哮喘（OA）最常见诱因。氧化应激导致甘露糖结合凝集素（MBL）激活，启动凝集素补体效应在调控炎性反应中起重要作用。为确定MBL2多态性与二异氰酸酯诱导的职业性哮喘（DI-OA）之间是否有基因关联，99例DI-OA患者，99例暴露的无症状对照（AECS）和144例未暴露的正常对照纳入本研究。MBL2启动子的三个多态性（-554 G> C，-431A> C和-225G>C）被进行基因分型，通过酶联免疫法测定血清MBL水平。启动子多态性变异的功能通过荧光素酶报告检测和电泳迁移率变动检测（EMSA）分析。与AEC组相比，DI-OA组的单倍型（ht）2[CAG]有显著的更高频率（P =0.044）。DI-OA患者中ht2 [CAG] 携带者比非携带者的PC20乙酰甲胆碱水平更显著降低（P <0.001）。携带ht1 [GAG]的DI-暴露主体（包括DI-OA患者和AECs）血清MBL水平显著更高（P = 0.028）。在人肝癌细胞（Hep3B细胞）中ht1 [GAG]相比ht2 [CAG] 具有显著增强荧光素酶活性（P = 0.002）。该EMSA分析表明， -554G探针相较-554C探针产生特异转移带。这些结果表明，MBL2基因的多态性降低了血清MBL水平从而，可能增加DI-暴露个体发展成为DI-OA的易感性。
 

（苏欣 审校）
Exp Mol Med. 2015 Apr 10;47:e157. doi: 10.1038/emm.2015.10.

Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupationalasthma.
 

MBL2

Kim SH1, Bae SJ1, Palikhe S2, Ye YM1, Park HS2.

Author information
 

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.
 

Exp Mol Med. 2015 Apr 10;47:e157. doi: 10.1038/emm.2015.10.