Association analysis of brain-derived neurotrophic factor gene polymorphisms in asthmatic families.
ABSTRACT A role for neuronal modulation of inflammation and airway hyper-responsiveness has been well described in asthma, and neurotrophins provide the link between inflammation and neuronal dysfunction. Brain-derived neurotrophic factor (BDNF) is an important mediator in this interaction. The aim of this study was to analyze the possible relationship between polymorphisms of the gene encoding BDNF and susceptibility to asthma.
341 families with at least 2 siblings with asthma were genotyped for 4 BDNF polymorphisms (rs6265, rs2030324, rs988748 and rs7124442).
Analysis by family-based association tests revealed no significant association between any polymorphisms analyzed and asthma susceptibility. Furthermore, BDNF polymorphism was not associated with asthma-related phenotypes such as FEV(1) % predicted, bronchial hyper-responsiveness, IgE level, asthma and atopy severity scores.
Our results suggest that genetic variation in the BDNF gene does not contribute significantly to asthma susceptibility or severity.
- Cytokine 01/1996; DOI:10.1109/CLEOE.1996.562510 · 2.87 Impact Factor
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ABSTRACT: 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. We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases. 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 and anova using SAS Genetics and spss. We identified nine polymorphisms with minor allele frequency >or=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). 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.Allergy 12/2009; 64(12):1790-4. DOI:10.1111/j.1398-9995.2009.02131.x · 6.00 Impact Factor
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ABSTRACT: Allergic asthma is associated with changes in neuronal control in the airways that modulate inflammation and airway hyperresponsiveness. The link between inflammation and neuronal dysfunction is provided mainly by neurotrophins, in particular Brain Derived Neurotrophic Factor (BDNF). In humans, significantly higher serum BDNF levels have been observed in asthmatic patients when compared with healthy subjects. BDNF levels are also significantly higher in untreated asthmatic patients in comparison to those treated with inhaled glucocorticoids and nonasthmatic controls. Allergic inflammation increases local BDNF production and its concentration correlates with clinical parameters of allergic airway dysfunction. The aim of this study was to analyze the possible association of BDNF gene polymorphism with susceptibility to asthma and disease severity. We analyzed 146 children diagnosed with asthma and 227 children from the control group. Genotyping of 4 BDNF polymorphisms (rs12273363, rs7124442, rs6265, and rs2030324) was done with use of PCR-RFLP and TaqMan SNP genotyping assay. Genetic association analysis was performed in Statistica. Linkage disequilibrium was determined with Haploview. Single marker analysis revealed a significant association of C allele of rs2030324 polymorphism with asthma susceptibility (P = 0.048). However, BDNF polymorphism was not associated with severe asthma. Strong linkage disequilibrium was observed between all of the BDNF polymorphisms analyzed grouped in one haplotype block. We found a significant association of TTGC haplotype with asthma (P = 0.025). Our results suggest that genetic variation in the BDNF gene may contribute to asthma susceptibility in case of rs2030324 polymorphism and TTGC haplotype, however it does not influence asthma severity.World Allergy Organization Journal 09/2010; 3(9):235-8. DOI:10.1097/WOX.0b013e3181eedb68