Broberg Karin, Tinnerberg Håkan, Axmon Anna, Warholm Margareta, Rannug Agneta, Littorin Margareta
Department of Occupational and Environmental medicine, Lund University, Sweden.
Environ Health. 2008 Apr 30;7:15. doi: 10.1186/1476-069X-7-15.
Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e.g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility.
Workers (N = 132) exposed to TDI and a non-exposed group (N = 114) were analyzed for genotype (metabolising genes: CYP1A12A, CYP1A12B, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO -463, NAT13, *4, *10, *11, *14, 15, NAT25, *6, 7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB105, TNF -308, TNF -863) and symptoms of the eyes, upper and lower airways (based on structured interviews).
For three polymorphisms: CYP1A12A, CYP1A12B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A12A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A12B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms (eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed,NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group.
Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non-TDI-related symptoms of the eyes and lower airways.
甲苯二异氰酸酯（TDI）是一种高反应性化合物，用于生产例如聚氨酯泡沫和涂料。已知TDI会引发呼吸道症状和疾病。由于TDI仅在一部分接触工人中引发症状，遗传因素可能在疾病易感性中起关键作用。
对接触TDI的工人（N = 132）和非接触组（N = 114）进行基因型分析（代谢基因：CYP1A12A、CYP1A12B、GSTM1O、GSTM3B、GSTP1 I105V、GSTP1 A114V、GSTT1O、MPO -463、NAT13、*4、*10、*11、*14、15、NAT25、*6、7、SULT1A1 R213H；免疫相关基因：CCL5 -403、HLA-DQB105、TNF -308、TNF -863）以及眼睛、上呼吸道和下呼吸道症状（基于结构化访谈）的分析。
对于三种多态性：CYP1A12A、CYP1A12B和TNF -308，在大多数所调查症状方面，存在与基因型和TDI接触状态之间相互作用一致的模式，尽管仅对某些症状达到统计学显著性：在接触TDI的工人中，CYP1A1变体携带者风险增加（CYP1A12A与眼部症状：变体携带者比值比2.0，95%置信区间0.68 - 6.1，相互作用p值0.048；CYP1A12B与喘息：IV携带者比值比 = 12，1.4 - 110，相互作用p值0.057）。携带TNF -308 A的接触TDI个体对大多数症状有保护作用，但未达到统计学显著性。然而，在非接触组中，TNF -308 A携带者表现出大多数症状的较高风险（眼部症状：变体携带者比值比 = 2.8，1.1 - 7.1，相互作用p值0.12；干咳比值比 = 2.2，0.69 - 7.2，相互作用p值0.036）。携带SULT1A1 213H的个体在接触组和非接触组中风险均降低。其他多态性与某些症状相关：在接触TDI的个体中，NAT1*10携带者眼部症状风险较高，CCL5 -403 AG + AA以及HLA-DQB1 *05携带者下呼吸道症状风险增加。GSTM1、GSTM3和GSTP1仅在非接触组中对下呼吸道症状有影响。
眼睛和下呼吸道症状似乎存在特定的基因 - TDI相互作用。结果表明眼睛和下呼吸道的TDI相关症状和非TDI相关症状存在不同机制。
