Association Analysis of Brain-Derived Neurotrophic Factor Gene Polymorphisms in Asthmatic Families

Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Third Department of Pediatrics, Poznan University of Medical Sciences, PL-60-572 Poznan, Poland.
International Archives of Allergy and Immunology (Impact Factor: 2.43). 04/2009; 149(4):343-9. DOI: 10.1159/000205580
Source: PubMed

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.

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    • "This polymorphism, along with other genetic variants in BDNF, has been associated with asthma in German children [37]. In contrast, other studies have suggested that though BDNF is a significant biomarker for allergic phenotypes, genetic variations in BDNF are not associated to allergic diseases [36] [39]. Thus the association of genetic polymorphisms in the BDNF gene with allergic diseases remains controversial. "
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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.
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