Abstract
with an asymptomatic cohort of HDI-exposed workers. Significant associations between genotype and occupational asthma were found only after adjustment for work-relevant diisocyanate exposure (ie, HDI vs TDI, MDI). The reason for restriction of this finding to the HDI-exposed population is unknown and may be an artifact of the greater numbers of HDI-exposed subjects available for statistical analysis. This study used a case-control design with a candidate gene approach. The rarity of diisocyanate asthma and the relatively small numbers of subjects able to be recruited compared with genetic studies of nonoccupational asthma are limitations of this study and hindrances to future replication studies. However, the issue of small group sizes could be counterbalanced by the ability to define theDA phenotype precisely by using objective SIC testswithwork-relevant diisocyanate chemicals. The role of these genotype combinations in the pathogenesis of DA is unknown and awaits functional characterization. Nevertheless, susceptibility genes associated with TH2cell differentiation (eg, IL4RA, IL13) and innate immunity (CD14) have been extensively investigated in nonoccupational asthma. The IL13 (R110Q) SNP has been associated with asthma and airway hyperresponsiveness, and IL4RAvariant Vand R alleles (I50Vand Q551R, respectively) have been associated with asthma and atopy.No suchassociationswere detected in the current study of workers not enriched with atopic subjects. In summary, we have confirmed a previous observation in expanded groups of workers: a reported association between genotype combinations associated with TH2 and innate immunity and diisocyanate-induced asthma caused by HDI. Replication of these results in other background populations will be necessary to define the possible value of these genetic markers for risk assessment. David I. Bernstein, MD Grace E. Kissling, PhD Gurjit Khurana Hershey, MD, PhD Berran Yucesoy, PhD Victor J. Johnson, PhD Andr e Cartier, MD Denyse Gautrin, PhD Joaquin Sastre, MD Louis-Philippe Boulet, MD Jean-Luc Malo, MD Santiago Quirce, MD Susan M. Tarlo, MBBS Stacy Langmeyer, MS Michael I. Luster, PhD Zana L. Lummus, PhD
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