Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study

• Main Authors: Rannug Agneta, Warholm Margareta, Axmon Anna, Tinnerberg Håkan, Broberg Karin, Littorin Margareta
• Format: Article
• Language: English
• Published: BMC 2008-04-01
• Series: Environmental Health
• Online Access: http://www.ehjournal.net/content/7/1/15

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Workers (N = 132) exposed to TDI and a non-exposed group (N = 114) were analyzed for genotype (metabolising genes: <it>CYP1A1</it>*2A, <it>CYP1A1</it>*2B, <it>GSTM1</it>*O, <it>GSTM3</it>*B, <it>GSTP1 </it>I105V, <it>GSTP1 </it>A114V, <it>GSTT1</it>*O, <it>MPO </it>-463, <it>NAT1</it>*3, *4, *10, *11, *14, *15, <it>NAT2</it>*5, *6, *7, <it>SULT1A1 </it>R213H; immune-related genes: <it>CCL5 </it>-403, <it>HLA-DQB1</it>*05, <it>TNF </it>-308, <it>TNF </it>-863) and symptoms of the eyes, upper and lower airways (based on structured interviews).</p> <p>Results</p> <p>For three polymorphisms: <it>CYP1A1</it>*2A, <it>CYP1A1</it>*2B, and <it>TNF </it>-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 <it>CYP1A1 </it>variant carriers had increased risk (<it>CYP1A1</it>*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68–6.1, p-value for interaction 0.048; <it>CYP1A1</it>*2B and wheeze: IV carriers OR = 12, 1.4–110, p-value for interaction 0.057). TDI-exposed individuals with <it>TNF</it>-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, <it>TNF </it>-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 <it>SULT1A1 </it>213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed,<it>NAT1*</it>10 carriers had a higher risk of eye symptoms and <it>CCL5 </it>-403 AG+AA as well as <it>HLA-DQB1 </it>*05 carriers displayed increased risk of symptoms of the lower airways. <it>GSTM1</it>, <it>GSTM3 </it>and <it>GSTP1 </it>only displayed effects on symptoms of the lower airways in the non-exposed group.</p> <p>Conclusion</p> <p>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.</p>