Research

IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood, a longitudinal study

Alireza Sadeghnejad¹ , Wilfried Karmaus² , S Hasan Arshad^3,4 , Ramesh Kurukulaaratchy^3,4 , Marianne Huebner⁵ and Susan Ewart⁶

¹  Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

²  Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, USA

³  The David Hide Asthma & Allergy Research Centre, St. Mary's Hospital, Isle of Wight, UK

⁴  IIR Research Division, School of Medicine, University of Southampton, Southampton, UK

⁵  Department of Statistics and Probability, Michigan State University, East Lansing, Michigan, USA

⁶  Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan, USA

author email corresponding author email

Respiratory Research 2008, 9:2doi:10.1186/1465-9921-9-2

Published:	10 January 2008

Abstract

Background

Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.

Methods

In the Isle of Wight birth cohort (UK, 1989–1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.

Results

Maternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).

Conclusion

This is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.