Abstract
BackgroundTobacco 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.MethodsIn 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.ResultsMaternal 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).ConclusionThis 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.
Highlights
Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing
Data on interleukin-13 gene (IL13) genotypes, exposure to tobacco smoke and wheeze phenotypes were available for 791 children
For IL13 genotypes, all five single nucleotide polymorphism (SNP) were in Hardy-Weinberg equilibrium and three of the SNPs demonstrated linkage disequilibrium based on D' (≥ 0.95) and r2 (≥ 0.89, Figure 1)
Summary
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. It has been suggested that the increased prevalence of asthma-related phenotypes over the last three decades is due to exposure to environmental factors [1]. Among such exposures, environmental tobacco smoke is regarded as an important risk factor for asthma-related phenotypes [2,3]. It has been reported that exposure to tobacco smoke during pregnancy was associated with a significantly higher production of IL-13 [11,12]. These observations suggest that part of the effect of exposure to tobacco on asthma-related phenotypes might be through cytokines
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