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Background Being born large for gestational age ( LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children. Objective We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association. Methods Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma. Results Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non- LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24). Conclusions We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma. [ABSTRACT FROM AUTHOR]

Background: Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain-derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation. Aim: We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases. Methods: The BDNF gene was screened for mutations in 80 chromosomes. Genotyping of six BDNF tagging polymorphisms was performed in a cross-sectional study population of 3099 children from Dresden and Munich (age 9–11 years, ISAAC II). Furthermore, polymorphisms were also investigated in an additional 655 asthma cases analysed with a random sample of 767 children selected from ISAAC II. Associations were calculated via chi-square test andanova using SAS Genetics andspss. Results: We identified nine polymorphisms with minor allele frequency ≥0.03, one of them leading to an amino acid change from Valine to Methionine. In the cross-sectional study population, no significant association was found with asthma or any atopic disease. However, when more severe asthma cases from the MAGIC study were analysed, significant asthma effects were observed with rs6265 (odds ratio 1.37, 95% confidence interval 1.14–1.64, P = 0.001), rs11030101 (OR 0.82, 95%CI 0.70–0.95, P = 0.009) and rs11030100 (OR 1.19, 95%CI 1.00–1.42, P = 0.05). Conclusions: As in previous studies, effects of BDNF polymorphisms on asthma remain controversial. The data may suggest that BDNF polymorphisms contribute to severe forms of asthma. [ABSTRACT FROM AUTHOR]

Background: Interleukin 15 (IL15) promotes activation and proliferation of CD8+ T cells and enhances the differentiation into Th2 cells. A previous study described five polymorphisms in the IL15 gene to be associated with asthma in a haplotype analysis. Aim: We selected HapMap tagging single nucleotide polymorphisms (SNPs) from IL15 to systematically investigate these IL15 associations in a large population-based sample. Methods: Genotyping of seven IL15 SNPs was performed using MALDI-TOF MS in a cross-sectional study population of 3099 children from Dresden or Munich (age 9–11 years). All children were phenotyped by standardized and validated protocols for atopic phenotypes. Effects of single SNPs and haplotypes were studied usingsas 9.1.3 andhaploview. Equivalence tests were performed to prove the significance of negative results. Results: Neither single IL15 polymorphisms nor haplotype analyses showed associations with asthma or atopy after correction for multiple testing. Conclusion: These results do not confirm previous case–control studies and suggest that IL15 gene variants do not play an important role in the development for asthma or other atopic disorders. [ABSTRACT FROM AUTHOR]

Background: Signal transducer and activator of transcription 1 (STAT1), an intracellular signal transducer and activator of transcription centrally involved in many inflammatory pathways, was recently suggested to play an important role in allergy related immune responses. Aim: Thus, we investigated the effect of polymorphisms in the STAT1 gene on the development of atopic sensitization and allergic diseases. Methods: Haplotype tagging single nucleotide polymorphisms (SNPs) previously described in the STAT1 gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology in a cross-sectional study population of 3099 German children recruited and phenotyped by the International Study of Asthma and Allergy in Childhood, phase II (ISAAC II). Effects of single SNPs and haplotypes were studied using SAS/Genetics and Haploview. Results: The polymorphism C39134A (rs3771300), located in a potentially cis acting regulatory element in STAT1 intron 24, was inversely related to atopy measured by skin prick test, total and specific serum IgE levels while no effect on atopic disease risk was observed. Conclusion: Our results indicate that STAT1 SNP C39134A may protect from atopic sensitization. Because of its location in a highly conserved noncoding sequence near a putative GATA3 binding site, this polymorphism represents an interesting target for further studies. [ABSTRACT FROM AUTHOR]