INTERACTION BETWEEN METABOLIC GENE POLYMORPHISMS AND VOCS IN CHILDHOOD ASTHMA

초록

Purpose: Asthma is a multifactorial disease caused by interaction between environmental factors and genetic susceptibility. Environmental exposure to volatile organic compounds(VOCs) has been associated with increased risk of asthma. This study was performed to evaluate the interaction between metabolic gene polymorphisms and environmental exposure to VOCs 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 VOCs, urinary hippuric acid and muconic acid were analyzed. 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. The level of urinary muconic acid was more increased in asthma patients than controls. There was no differences between asthma patients and controls in gene polymorphisms of CYP1A1 and CYP2E1. Combinations of CYP 2E1 gene polymorphisms and high concentration of muconic acid were associated with significantly increased risk for development of asthma(OR 6.0 95% CI = 1.2-35.3).Combination of GSTM1 gene deletion and high concentration of muconic acid were associated with significantly increased risk for development of asthma(OR 7.9 95% CI = 1.2-53.0). Conclusions: The risk of asthma is significantly increased by interaction of exposure to VOCs and their metabolic gene polymorphisms. The gene-environment interaction might play an important role in individual variation for development of asthma