Interaction between metabolic gene polymorphisms and environmental factors in childhood asthma

초록

Objective: Asthma is a multifactorial disease caused by interaction between environmental factors and genetic susceptibility. Environmental exposure to polycyclic aromatic hydrocarbons(PAHs) has been associated with increased risk of asthma. Also there were a few reports that suggest association between metabolic gene polymorphisms and asthma. So we wanted to evaluate the interaction between metabolic gene polymorphisms and environmental exposure to PAHs on childhood asthma. Methods: Subjects were 30 children with asthma and 30 controls. Polymorphisms in the CYP1A1, CYP2E1, GSTM1, GSTT1 and GSTP1 genes were analyzed. As a biomarker of exposure to PAHs, urinary 1-hydroxypyrene(1-OHP) and 2-naphthol(2-NAP) were analyzed. Exposure levels measured by biomarkers were categorized into tertiles. Subjects were grouped based on genotype by exposure categories. The odds ratios were estimated by multiple logistic regression models, adjusting for age and sex(SAS v8.1). Results: Risk of asthma was increased in polymorphisms in GSTM1 and GSTT1 genes with OR 1.71, 1.50, respectively. For the genes of CYP1A1 and CYP2E1, there was no difference between asthma patients and controls. The level of urinary 1-OHP was more increased in asthma patients than control. There was strong interaction between GSTM1 gene deletion and concentration of 1-OHP. Conclusion: We suggest that the risk of asthma increased by interaction of exposure to PAHs and their metabolic gene polymorphisms. Gene-environment interaction might play a important role in individual variation of asthma.