RESUMEN
BACKGROUND: Atopic eczema is characterized by Th2-dominant immunity with the cytokine interleukin 13 and the transcription factor GATA binding protein 3 playing a critical role. OBJECTIVES: We assessed the association of polymorphisms in the IL13 and GATA3 genes with childhood eczema. METHODS: A birth cohort (n = 1456) was established on the Isle of Wight in 1989 and followed at the ages of 1 (n = 1167), 2 (n = 1174), 4 (n = 1218) and 10 years (n = 1373) to determine the prevalence of allergic disease including eczema. At 4 and 10 years, skin prick testing was performed. Whole blood samples (n = 923) were obtained at the 10-year assessment, stored frozen, and genotyped. Five polymorphisms from IL13 and seven from GATA3 were genotyped for this analysis. Repeated measurement analyses were conducted for the occurrence of eczema at ages 1, 2, 4 and 10 years. All analyses were adjusted for maternal and paternal eczema, low birth weight (< 2500 g), breastfeeding >or= 3 months and age. RESULTS: IL13 was not associated with childhood eczema. For GATA3, the single nucleotide polymorphism (SNP) rs2275806 (promoter region) showed an increased odds ratio for atopic eczema independent of whether the comparison group had a positive skin prick test. The SNP rs444762 (intron 3 region) was associated with atopic eczema in comparison with children without eczema. The increased relative risks remained significant after adjustment for multiple testing only for rs2275806 (P < 0.05). CONCLUSIONS: A SNP in GATA3 is associated with atopic eczema. This finding highlights the importance of GATA3 as an immune-modulating gene in atopic eczema.
Asunto(s)
Dermatitis Atópica/genética , Factor de Transcripción GATA3/genética , Interleucina-13/genética , Polimorfismo de Nucleótido Simple/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Oportunidad Relativa , Fenotipo , Pruebas Cutáneas/métodos , Regulación hacia ArribaRESUMEN
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 (n = 921) 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.
Asunto(s)
Asma/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Polimorfismo de Nucleótido Simple/genética , Efectos Tardíos de la Exposición Prenatal , Contaminación por Humo de Tabaco/efectos adversos , Hiperreactividad Bronquial/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Volumen Espiratorio Forzado/genética , Genotipo , Humanos , Lactante , Recién Nacido , Desequilibrio de Ligamiento , Estudios Longitudinales , Embarazo , Riesgo , Reino Unido , Capacidad Vital/genéticaRESUMEN
BACKGROUND: Evidence suggests that a raised level of cord serum IgE (CS-IgE) is a risk factor for allergic sensitisation. However, whether CS-IgE is a risk for asthma is controversial. A study was undertaken to investigate the association between CS-IgE levels and allergic sensitisation at 4 and 10 years of age and asthma at ages 1-2, 4 and 10. METHODS: CS-IgE was available for 1358 of 1456 children born between 1989 and 1990. The cohort was evaluated for allergic diseases at ages 1, 2, 4 and 10 years. Skin prick tests for six allergens were performed on 981 children at age 4 and 1036 at age 10. Asthma was defined based on a physician's diagnosis. Using logistic regression analysis, the risk of asthma and allergic sensitisation for raised levels of CS-IgE (> or =0.5 kU/l) was estimated. RESULTS: At ages 4 and 10 years 20.2% and 27.0% of children, respectively, had allergic sensitisation. The risk of allergic sensitisation was significantly associated with raised CS-IgE levels at ages 4 (OR 2.29) and 10 years (OR 1.73). The prevalence of asthma was 10.3% at age 1-2, 15.2% at age 4, and 12.8% at age 10. CS-IgE was not associated with asthma at age 1-2 and 4 but showed an increased relative risk at age 10 (OR 1.66, 95% CI 1.05 to 2.62). The association was stronger in children who did not develop allergic sensitisation at age 4 or 10 (OR 3.35, 95% CI 1.41 to 7.93). CONCLUSIONS: Raised cord serum IgE is a risk factor for allergic sensitisation at ages 4 and 10 years. This is the second study suggesting that CS-IgE is also a risk factor for asthma at age 10, probably related to the late onset of asthma. This association is not necessarily mediated by allergic sensitisation.
Asunto(s)
Sangre Fetal/química , Hipersensibilidad/sangre , Inmunoglobulina E/sangre , Asma/sangre , Asma/etiología , Niño , Preescolar , Femenino , Humanos , Hipersensibilidad/etiología , Masculino , Factores de Riesgo , Pruebas CutáneasRESUMEN
BACKGROUND: Identifying the protective effect of a higher number of siblings is a significant finding in understanding the aetiology of allergic sensitization, asthma, eczema, and hayfever. Knowledge about causes behind the sibling effect may allow us to prevent atopic manifestations. OBJECTIVE: We tested the hypothesis that rising order of live offspring increases maternal immune tolerance (immune non-reactivity) against allergens. To this end, we investigated whether maternal IgE levels are associated with the number of live offspring. METHODS: In a cohort of 1456 newborns recruited between January 1989 and February 1990 on the Isle of Wight, UK, we determined maternal and cord serum IgE, and the order of live offspring. The data were analysed by means of linear and path analysis. RESULTS: Maternal and cord serum IgE were available in 820 mother-infant pairs with birth order information. We found that the number of live offspring significantly reduces maternal IgE. The decline was more prominent in mothers with atopy (n=268). The geometric means of IgE after the first, second, and third or higher delivery were 74.4, 66.6, and 43.0 kU/L, respectively. Findings of path analysis suggest a significant direct effect of birth order on maternal IgE, but no direct effect of birth order on cord serum IgE. CONCLUSION: The findings support that maternal immune tolerance against allergens may increase with increasing order of live offspring and thus pass on a lower risk of developing atopy in children of higher birth order.