ISEE/ISEA 2006 Conference Abstracts Supplement: Symposium Abstracts: Abstracts
*Department of Public Health Sciences, University of California; Davis; †Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR and Health Institute of Central Bohemia, Prague, Czech Republic; and ‡Department of Pediatrics, University of California, Davis, California
Bronchitis in early childhood is a common occurrence. It can reflect both viral and bacterial infection as well as hypersensitivity involving wheeze. We examined genetic polymorphisms and gene–environment interactions in relation to early childhood bronchitis.
A birth cohort comprising a probability sample of 20% of deliveries between May 1994 and March 1999 in 2 districts in the Czech Republic was followed up at 3 to 4.5 years of age. Pediatric records were abstracted for all illnesses. Bronchitis was defined as a physician diagnosis of J20 (acute bronchitis). Parents completed questionnaires at birth and at follow up regarding sociodemographics, lifestyle, indoor air pollution sources, breast-feeding, day care, and other factors potentially related to respiratory illnesses. PCR-RFLP techniques were used for genotype analysis of xenobiotic metabolizing (GSTM1, GSTT1, and so on) and DNA repair genes (XPD-6, XPD-23) in samples of fetal tissue from placentas of 800 births. Poisson regression was used to model the number of episodes of bronchitis during the first 2 years of life in relation to child's genotype, with adjustment for ethnicity, maternal smoking, child's sex, mother's age and education, season of birth, and use of coal for home heating or cooking. Additionally, XPD-6 was examined for modification of the effects of acute air pollution in a repeated-measures logistic regression analysis.
More than 60% of the children experienced one or more episodes of bronchitis in the first 2 years of life. Xenobiotic metabolizing genes did not predict the number of bronchitis events, but XPD-6 polymorphisms did. Those with the XPD-6 AA genotype (40% of children) experienced bronchitis more frequently than the homozygous CC and heterozygous children combined (relative risk = 1.45, 95% confidence interval [CI]: 1.36–1.55). Those with the CC genotype had a similar risk to the heterozygotes. Genotype did not modify the effects of ambient air pollution.
Discussion and Conclusion:
XPD genes encode for nucleotide excision repair and basal transcription, and their transcription may be regulated by insulin. In our data, the C-allele of XPD-6 appears to confer some protection against bronchitis in early childhood after adjusting for ethnicity and other factors. Neither XPD-6 nor XPD-23 renders children more susceptible to short-term respiratory effects of ambient particles or PAHs. Although studied mainly for their involvement in cancer risk, XPD genes may play a role in immune competence.