The HLA DRB1*1501-DQB1*0602-DPB1*0501 Haplotype Is a Risk Factor for Toluene Diisocyanate-Induced Occupational Asthma
The HLA DRB1*1501-DQB1*0602-DPB1*0501 Haplotype Is a Risk Factor for Toluene Diisocyanate-Induced Occupational Asthma
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DOI：
10.1159/000218118
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发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Park, Hae-Sim
中科院分区：
文献类型：
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作者：
Choi, Jeong-Hee;Lee, Kyung-Wha;Park, Hae-Sim
背景：尽管甲苯二异氰酸酯 (TDI) 诱发的职业性哮喘 (TDI-OA) 的发病机制尚不完全清楚，但一些研究表明了免疫机制，包括特异性 IgE 反应。一些研究表明，在西方国家，人类白细胞抗原 (HLA) 与 TDI 诱发的哮喘相关，但这是首次使用高分辨率分析对亚洲 HLA I 类和 II 类等位基因与 TDI 诱发的哮喘患者之间的关联进行研究。方法：纳入 TDI-OA 患者 (n=84)、无症状暴露对照 (AEC, n=47) 和未暴露正常对照 (NC, n=127)。通过直接 DNA 测序分析进行 HLA I 类和 II 类基因分型。通过 ELISA 测量针对蒸气型 TDI-白蛋白缀合物的特异性血清 IgE 抗体。结果：等位基因频率与 TDI-OA 表型之间没有显着相关性。然而，TDI-OA 患者 (19%) 中 HLA DRB1*1501-DQB1*0602-DPB1 *0501 单倍型的频率显着高于 AEC（2.1%，p=0.007，OR 4.429，CI 1.497-13.103）或 NC（3.1%，p）
Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n=84), asymptomatic exposed controls (AECs, n=47) and unexposed normal controls (NCs, n=127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602-DPB1 *0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p=0.007, OR 4.429, CI 1.497-13.103) or NC (3.1%, p