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


METHODS
Workers (N = 132) exposed to TDI and a non-exposed group (N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 I105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1*05, TNF -308, TNF -863) and symptoms of the eyes, upper and lower airways (based on structured interviews).


RESULTS
For three polymorphisms: CYP1A1*2A, CYP1A1*2B, 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 (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B 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.


CONCLUSIONS
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.
Broberg
Karin
K
Department of Occupational and Environmental medicine, Lund University, Sweden. karin.broberg@med.lu.se
Tinnerberg
Håkan
H
Axmon
Anna
A
Warholm
Margareta
M
Rannug
Agneta
A
Littorin
Margareta
M
D000293:Adolescent; D000328:Adult; D000395:Air Pollutants, Occupational / Q000032:analysis / Q000097:blood / Q000633:toxicity* / Q000652:urine; D000485:Allergens / Q000276:immunology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D005128:Eye Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D020641:Polymorphism, Single Nucleotide; D012140:Respiratory Tract Diseases / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000652:urine; D013548:Sweden / Q000453:epidemiology; D014051:Toluene 2,4-Diisocyanate / Q000032:analysis / Q000097:blood / Q000633:toxicity* / Q000652:urine
D000395:Air Pollutants, Occupational; D000485:Allergens; D015415:Biomarkers; D014051:Toluene 2,4-Diisocyanate