Interleukin-1R antagonist gene and pre-natal smoke exposure are associated with childhood asthma

Abstract

The interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory cytokine. In the present study, association of the human IL1RN gene polymorphisms with asthma, bronchial hyperresponsiveness and forced expiratory volume in one second/forced vital capacity ratio was tested and the data was stratified by environmental tobacco smoke exposure in order to investigate a gene-smoking interaction.In an unselected subset (n5921) of the Isle of Wight birth (UK) cohort, which has previously been evaluated for asthma and related manifestations at ages 1, 2, 4 and 10 yrs, three IL1RN single nucleotide polymorphisms (SNP) were genotyped. Logistic regression and repeated measurement models for tests of association using a representative SNP rs2234678 were used, as all SNPs tested were in strong linkage disequilibrium.In the overall analysis, the SNP rs2234678 was not associated with asthma. However, in the stratum with maternal smoking during pregnancy the rs2234678 GG genotype significantly increased the relative risk of asthma in children, both in analyses of repeated asthma occurrences and persistent asthma.In conclusion, the present results show that in the first decade of life, the gene-environment interaction of the interleukin-1 receptor antagonist gene polymorphism rs2234678 and maternal smoking during pregnancy increased the risk for childhood asthma.

Gene by Environment Interaction in Asthma

“…We can draw no firm conclusions about interactions between specific genetic polymorphisms and environmental tobacco smoke using the available body of literature (Table 1) (11,28,29,45,49,50,52,64,67,70,71,74,(87)(88)(89)92). Neither do we feel confident that, using the published literature, we can propose specific genetic polymorphisms that definitely interact with ambient air pollution to produce For studies of continuous outcomes the total N is given.…”

Étude d'association entre l'asthme et les gènes associés à ce phénotype et à la pollution de l'air, dans un échantillon d'asthme provenant d'un environnement régional caractérisé par différentes industries /

“…Des gènes codant pour des molécules impliquées dans la réponse immunitaire ont aussi été associés à l'asthme en lien avec l'exposition à la fumée de cigarette. Des gènes comme IL 13 (41), IL1RN (42), Transforming Growth Factor Beta 1 (TGFB1) (43), CD14 (44) et Tumor Necrosis Factor (TNF) (45) ont été associés plus fortement à l'asthme lorsqu'exposés à la fumée du tabac. De plus, dans certaines études, l'association de ces gènes a été seulement observée lorsqu'il y avait exposition à la fumée du tabac in utero ou en bas âge (voir Tableau 2).…”

An Exploration of Gene–Environment Interaction and Asthma in a Large Sample of 5-Year-Old Dutch Twins

“…Asthma research with measured genotypes has provided evidence for gene-environment interaction. For example, several studies found that the effect of genotype on asthma was modified by prenatal exposure to tobacco smoke or exposure in early life (Colilla et al, 2003;Dizier et al, 2007;Meyers et al, 2005;Ramadas et al, 2007).…”

“…Results from human linkage and association studies for asthma also provide evidence for gene-environment interaction (Colilla et al, 2003;Dizier et al, 2007;Meyers et al, 2005;Ramadas et al, 2007). For example, Ramadas et al (2007) examined the interleukin-1 receptor antagonist (IL1RN) which is a potent anti-inflammatory cytokine.…”

“…For example, Ramadas et al (2007) examined the interleukin-1 receptor antagonist (IL1RN) which is a potent anti-inflammatory cytokine. In a group of 921 children, no evidence was found for an association of asthma with a SNP in the Il1RN gene.…”