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. 2008 Jan 10;9(1):2.
doi: 10.1186/1465-9921-9-2.

IL13 Gene Polymorphisms Modify the Effect of Exposure to Tobacco Smoke on Persistent Wheeze and Asthma in Childhood, a Longitudinal Study

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Free PMC article

IL13 Gene Polymorphisms Modify the Effect of Exposure to Tobacco Smoke on Persistent Wheeze and Asthma in Childhood, a Longitudinal Study

Alireza Sadeghnejad et al. Respir Res. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Using the Haploview program [32], three single nucleotide polymorphisms of the interleukin 13 gene appeared to be in a block. r2, a pair wise linkage disequilibrium determinant [33], is shown.
Figure 2
Figure 2
The vertical axis is the percentage of early-onset persistent wheezers divided by the sum of early-onset persistent wheezers and non-wheezers (n = 791). For each genotype strata, reference was ETS-0. *, p value < 0.05; **, p value < 0.001. ETS-0, mothers did not smoke during pregnancy and children were not exposed to household ETS; ETS-1, mothers did not smoke during pregnancy, but children were exposed to household ETS; ETS-2, mothers smoked during pregnancy and children were exposed to household ETS. SNP, single nucleotide polymorphism; rs1800925, rs2066960, rs1295686, rs20541 and rs1295686 are five SNPs within the interleukin13 gene. SNPs rs1295686, rs20541, and rs1295686 were in a block. Therefore haplotype analysis was based on SNPs rs1800925, rs2066960, and rs20541. # The most common haplotype pair, CCG/CCG, constructed based on SNPs rs1800925, rs2066960, and rs20541, using PHASE 2.0.2 software [34].

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