儿童喘息中早期母亲吸烟与 TNF 和 GSTP1 变异体的相互作用。

Interaction between early maternal smoking and variants in TNF and GSTP1 in childhood wheezing.

机构信息

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Clin Exp Allergy. 2010 Mar;40(3):458-67. doi: 10.1111/j.1365-2222.2010.03452.x.

DOI:10.1111/j.1365-2222.2010.03452.x

PMID:20210814

Abstract

BACKGROUND

Children exposed to tobacco smoke early in life have a higher risk of wheeze. Individual susceptibility may depend on genetic factors.

OBJECTIVE

We studied whether variations in single nucleotide polymorphisms (SNPs) in the TNF, glutathione S transferase P1 (GSTP1) and beta2-adrenoreceptor (ADRB2) genes modify the effect of early maternal smoking on the development of childhood asthma, wheeze and allergic sensitization.

METHODS

In the Swedish prospective birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) (n=4089), data collection included questionnaires to measure tobacco smoke exposure and clinical outcomes up to age 4 and medical examinations with blood sampling for specific IgE measurements and genotyping. We defined early maternal smoking as daily smoking by the mother during pregnancy and/or postnatally. We investigated five TNF, six GSTP1 and three ADRB2 SNPs in 982 selected wheezers and non-wheezers.

RESULTS

An interaction with early maternal smoking was found for three TNF SNPs (-857C/T, Intron 1, Intron 3) with respect to early wheeze (up to 2 years of age). For example, the odds ratio (OR) for developing early wheeze related to early maternal smoking was 2.4 [95% confidence interval (CI) 1.6-3.7] in children with a wild-type CC homozygote genotype of the TNF-857 SNP, while no tobacco-related risk was seen in children carrying the rare T allele. A clear dose response was observed in children with the CC genotype, with an OR of 1.3 (95% CI 1.1-1.5) per each additional pack per week smoked by the mother during pregnancy. A suggestive interaction with early maternal smoking was also seen for three GSTP1 SNPs (Intron 5, Intron 6 and Ile105Val) with respect to transient wheeze, but not for ADRB2 and wheeze phenotypes. No effect modifications were observed for allergic sensitization.

CONCLUSION

Our results suggest that the risk of early childhood wheeze associated with early maternal smoking may be modified by TNF and GSTP1 polymorphisms.

摘要

背景

儿童在生命早期接触烟草烟雾，其喘息的风险更高。个体易感性可能取决于遗传因素。

目的

我们研究了 TNF、谷胱甘肽 S 转移酶 P1（GSTP1）和β2-肾上腺素能受体（ADRB2）基因中的单核苷酸多态性（SNP）是否会改变早期母亲吸烟对儿童哮喘、喘息和过敏敏化发展的影响。

方法

在瑞典前瞻性出生队列 BAMSE（儿童、过敏、环境、斯德哥尔摩、流行病学调查）（n=4089）中，数据收集包括问卷调查，以测量烟草烟雾暴露和临床结果，直至 4 岁，以及医疗检查，包括血液采样以测量特异性 IgE 水平和基因分型。我们将母亲在怀孕期间和/或产后的每日吸烟定义为早期母亲吸烟。我们在 982 名选定的喘息者和非喘息者中研究了五个 TNF、六个 GSTP1 和三个 ADRB2 SNPs。

结果

我们发现三个 TNF SNP（-857C/T、内含子 1、内含子 3）与早期喘息（2 岁以下）与早期母亲吸烟存在交互作用。例如，与早期母亲吸烟相关的早期喘息风险比（OR）在 TNF-857 SNP 野生型 CC 纯合子基因型的儿童中为 2.4（95%置信区间[CI]1.6-3.7），而在携带罕见 T 等位基因的儿童中则没有发现与烟草相关的风险。在 CC 基因型的儿童中观察到明显的剂量反应，母亲在怀孕期间每周每增加一包烟，OR 为 1.3（95%CI1.1-1.5）。对于 GSTP1 三个 SNP（内含子 5、内含子 6 和 Ile105Val），我们也观察到了与短暂喘息的提示性交互作用，但对于 ADRB2 和喘息表型则没有。对于过敏敏化，未观察到效应修饰。