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: 2.67). 04/2009; 149(4):343-9. DOI: 10.1159/000205580
Source: PubMed


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 diseases affect more than 25% of the world population and result from a complex interplay between genetic and environmental factors. Recent evidence has shown that BDNF (Brain Derived Neurotrophic Factor) could serve as an important marker of allergic disease. Increased levels of BDNF in blood, bronchoalveolar lavage fluid and nasal lavage fluid positively correlate with disease activity and severity in patients with allergic rhinitis (AR), asthma and atopic eczema. However, reports on the association between genetic variation in BDNF and allergic disease have been controversial. This study therefore aims to clarify the relationship between single nucleotide polymorphisms (SNPs) in BDNF and a genetic predisposition to AR and asthma in an ethnic Chinese population of Singapore. Volunteers with a self-reported history of asthma (718 subjects) or a history of AR as determined by a researcher-administered questionnaire (795 subjects) were used in this study, alongside controls with no personal or family history of allergy (717 subjects). The association results identified a significant association for the tagSNP rs10767664 with a significant PDominant=0.0007 and OR=1.3 for AR and PDominant=0.0005 and OR=1.3 for asthma (using a dominant model of association). The haplotype based analysis also identified a significant association further confirming the single SNP association. The SNP rs10767664 is strongly linked (r2=0.95) to the functional polymorphism rs6265 (Val66Met), which has previously been reported to be associated to allergic phenotypes and also shown to affect BDNF expression. BDNF is a therefore a key molecular player in allergy. Further studies on polymorphisms within BDNF may shed light on its role in the pathogenesis of allergic diseases and potentially serve as biomarkers for allergic disease.
    Cytokine 06/2011; 56(2):218-23. DOI:10.1016/j.cyto.2011.05.008 · 2.66 Impact Factor
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    • "In this block we found that TTGC haplotype was associated with higher risk of developing asthma in our population. Such an association was not found previously [12]. This may result not only from the differences in sample size, but also from ethnic disparities between the Polish and British samples. "
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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
  • Cytokine 01/1996; DOI:10.1109/CLEOE.1996.562510 · 2.66 Impact Factor
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