IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood, a longitudinal study.
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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DOI：
10.1186/1465-9921-9-2
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发表时间：
2008-01-10
影响因子：
5.8
通讯作者：
Ewart, Susan
中科院分区：
文献类型：
--
作者：
Sadeghnejad, Alireza;Karmaus, Wilfried;Arshad, S. Hasan;Kurukulaaratchy, Ramesh;Huebner, Marianne;Ewart, Susan
吸烟和遗传易感性是哮喘和喘息的危险因素。本研究的目的是探讨是否存在白介素-13基因（IL13）多态性和吸烟对儿童持续性喘息和哮喘的联合影响。在英国，1989-1999年的莱特岛出生队列中，对5个IL13单核苷酸多态性rs1800925 （-1112C/T）、rs2066960、rs1295686、rs20541 （R130Q）和rs1295685进行基因分型。父母被问及他们的孩子在1岁、2岁、4岁和10岁时在过去的12个月里是否有过喘息。在4岁前报告有喘息并在10岁时也有喘息的儿童被归类为早发性持续性喘息表型；非喘息者在10岁前从不喘息。持续性哮喘被定义为在生命的前四年和10岁时被诊断为哮喘。采用Logistic回归方法对791例信息完整的患儿资料进行分析。潜在的混杂因素包括性别、出生体重、母乳喂养的持续时间以及怀孕期间家里的猫或狗。孕期吸烟与早发性持续性喘息相关（OR 2.93, p < 0.0001）；IL13的多态性不存在（OR为1.15,p = 0.60）。然而，母亲在怀孕期间吸烟对具有常见IL13单倍型对的儿童的影响比没有吸烟的儿童更强（OR分别为5.58和1.29；相互作用p = 0.014）。单SNP分析显示rs20541具有相似的统计学意义（交互作用p = 0.02）。在持续性儿童哮喘中观察到类似的结果（相互作用p = 0.03）。这是第一份显示子宫内暴露于吸烟和il - 13对儿童哮喘表型综合影响的报告。研究结果强调，基因研究需要将环境暴露考虑在内，因为它们可能解释相互矛盾的发现。
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. 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. 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). 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.
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影响因子：
6.1
作者：
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通讯作者：
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