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: In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target.Pharmacology [?] Therapeutics 07/2014; DOI:10.1016/j.pharmthera.2014.02.006 · 7.75 Impact Factor
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ABSTRACT: Objectives Bronchial asthma is a chronic respiratory disease characterized by airway inflammation. There is increasing evidence that neurotrophins play an important role in the development and maintenance of neurogenic airway inflammation in chronic allergic diseases.Working HypothesisBrain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and has several important functions in the airways. There are only a few reports on the association between genetic variations in the BDNF gene and various allergic diseases, and the results are generally conflicting. Therefore, we aimed to study the functional polymorphism Val66Met (also called rs6265 or G196A) in the BDNF gene in a group of asthmatic children and healthy controls.Study Design, Patient-Selection, and MethodologyWe studied 248 asthmatic patients (aged 12.28 ± 0.24 years) and 249 healthy children (aged 13.14 ± 0.48 years). Analysis of the Val66Met polymorphism of the BDNF gene was performed by polymerase chain reaction (PCR) and PCR products were digested by PmlI.ResultsThe prevalence of the Val66Met polymorphisms (Val/Val, Val/Met, and Met/Met) was 61.7%, 33.5%, and 4.8% in asthmatics, respectively, and 47.0%, 51.8%, and 1.2% in healthy subjects, respectively. We observed a significant association of the Met/Met variant genotype with asthmatics (OR = 4.17, 95% CI = 1.16–14.96, P = 0.018). The Val/Met genotype was protective against bronchial asthma (OR = 0.69, 95% CI = 0.48–0.99, P = 0.045), especially in girls (OR = 0.34, 95% CI = 0.20–0.59, P = 0.001).Conclusion Specific BDNF gene polymorphism may contribute to bronchial asthma susceptibility. Our study suggested the positive association between selected functional BDNF polymorphism (rs6265) and asthma in children. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.Pediatric Pulmonology 05/2014; DOI:10.1002/ppul.23065 · 2.30 Impact Factor