This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200704-561OCv1 176/12/1192    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salam, M. T. Articles by Gilliland, F. D. Search for Related Content PubMed PubMed Citation Articles by Salam, M. T. Articles by Gilliland, F. D.

Transforming Growth Factor-β1 C-509T Polymorphism, Oxidant Stress, and Early-Onset Childhood Asthma

¹ Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California

Correspondence and requests for reprints should be addressed to Frank D. Gilliland, M.D., Ph.D., Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033. E-mail: gillilan{at}usc.edu

Rationale: Transforming growth factor (TGF)-β1 is involved in airway inflammation and remodeling, two key processes in asthma pathogenesis. Tobacco smoke and traffic emissions induce airway inflammation and modulate TGF-β1 gene expression. We hypothesized that the effects of functional TGF-β1 variants on asthma occurrence vary by these exposures.

Objectives: We tested these hypotheses among 3,023 children who participated in the Children's Health Study.

Methods: Tagging single-nucleotide polymorphisms rs4803457 C>T and C-509T (a functional promoter polymorphism) accounted for 94% of the haplotype diversity of the upstream region. Exposure to maternal smoking in utero was based on smoking by biological mother during pregnancy. Residential distance from nearest freeway was calculated based on residential address at study entry.

Measurements and Main Results: Children with the –509TT genotype had a 1.8-fold increased risk of early persistent asthma (95% confidence interval [CI], 1.11–2.95). This association varied marginally significantly by in utero exposure to maternal smoking. Compared with children with the –509CC/CT genotype with no in utero exposure to maternal smoking, those with the –509TT genotype with such exposure had a 3.4-fold increased risk of early persistent asthma (95% CI, 1.46–7.80; interaction, P = 0.11). The association between TGF-β1 C-509T and lifetime asthma varied by residential proximity to freeways (interaction P = 0.02). Children with the –509TT genotype living within 500 m of a freeway had over three-fold increased lifetime asthma risk (95% CI, 1.29–7.44) compared with children with CC/CT genotype living > 1500 m from a freeway.

Conclusions: Children with the TGF-β1 –509TT genotype are at increased risk of asthma when they are exposed to maternal smoking in utero or to traffic-related emissions.

Key Words: maternal smoking • traffic • asthma • genetics • gene–environment interaction • association study

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The associations between transforming growth factor (TGF)-β1 C-509T promoter polymorphism and childhood asthma have been inconsistent, which could in part be explained by differences in environmental exposures (traffic and tobacco smoke) that affect TGF-β1 expression. What This Study Adds to the Field Children with the TGF-β1 –509TT genotype are at higher risk of asthma occurrence if they live near a freeway or were exposed to tobacco smoke in utero.

 

This article has been cited by other articles:

				W. C. Moore Update in Asthma 2007 Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1068 - 1073. [Full Text] [PDF]

				J. M. Collaco, L. Vanscoy, L. Bremer, K. McDougal, S. M. Blackman, A. Bowers, K. Naughton, J. Jennings, J. Ellen, and G. R. Cutting Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease JAMA, January 30, 2008; 299(4): 417 - 424. [Abstract] [Full Text] [PDF]