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

Szczepankiewicz, Aleksandra; Rose-Zerilli, Matthew; Barton, Sheila J.; Holgate, Stephen T.; Holloway, John W.

doi:10.1159/000205580

Cited by 14 publications

(14 citation statements)

References 68 publications

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“…Previous studies investigating the impact of genetic variation in BDNF have shown conflicting results [7,11,12]. Negative association results presented here for 3 BDNF polymorphisms (rs12273363, rs7124442, rs6265) are consistent with those obtained in a German cohort[11] and also with data published for a large British cohort of asthmatic siblings [12].…”

Section: Discussionsupporting

confidence: 89%

Association of BDNF Gene Polymorphism With Asthma in Polish Children

Szczepankiewicz

Bręborowicz

Sobkowiak

et al. 2010

World Allergy Organization Journal

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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.

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Section: Discussionsupporting

confidence: 89%

Association of BDNF Gene Polymorphism With Asthma in Polish Children

Szczepankiewicz

Bręborowicz

Sobkowiak

et al. 2010

World Allergy Organization Journal

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“…Previous studies have investigated the association of the rs7124442 SNP to eating disorders, cognitive abilities in the elderly, major depression, susceptibility to asthma, Parkinson's disease, autism, Alzheimer's disease and migraine [67], [68], [69], [70], [71], [72], [73]. The only significant associations identified were to eating disorders and high plasma BDNF levels [67] as well as a significant negative influence of TT genotype on treatment response to SSRI, opposed to CC [69].…”

Section: Discussionmentioning

confidence: 99%

BDNF Polymorphism Predicts General Intelligence after Penetrating Traumatic Brain Injury

et al. 2011

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Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injured controls (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10–15 years post-injury, and Phase III (30–35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery.

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“…With evidence for BDNF expression and signaling in airway innervation, epithelium and smooth muscle there is obviously significant interest in the potential role for targeting NTs such as BDNF in asthma (Abram et al, 2009; Bennedich Kahn et al, 2008; Dagnell et al, 2007; Freund-Michel and Frossard, 2008; Frossard et al, 2004; Nassenstein et al, 2006; Nockher and Renz, 2006; Prakash et al, 2009; Renz et al, 2004; Rochlitzer et al, 2006). In this regard, there is some evidence for an association between BDNF and asthma, particularly in children as well as increased asthma association with a variant of the BDNF gene (Andiappan et al, 2011; Koskela et al, 2010; Szczepankiewicz et al, 2007; Szczepankiewicz et al, 2010; Szczepankiewicz et al, 2009; Yinli et al, 2013; Zeilinger et al, 2009). Furthermore, in humans as well as in mouse models of asthma, allergen challenge increases NGF and BDNF levels in bronchoalveolar lavage fluid (Braun et al, 1999; Virchow et al, 1998).…”

Section: Bdnf and Asthmamentioning

confidence: 99%

Brain-derived neurotrophic factor in the airways

Prakash

Martin

2014

Pharmacology & Therapeutics

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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.

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

Cited by 14 publications

References 68 publications

Association of BDNF Gene Polymorphism With Asthma in Polish Children

Association of BDNF Gene Polymorphism With Asthma in Polish Children

BDNF Polymorphism Predicts General Intelligence after Penetrating Traumatic Brain Injury

Brain-derived neurotrophic factor in the airways

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