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Association of BDNF gene polymorphism with asthma in polish children.

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.

SUBMITTER: Szczepankiewicz A

PROVIDER: S-EPMC3651092 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Association of BDNF gene polymorphism with asthma in polish children.

Szczepankiewicz Aleksandra A Bręborowicz Anna A Sobkowiak Paulina P Popiel Anna A

The World Allergy Organization journal 20100901 9

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 ...[more]

PMID: 23282800

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Project description:PurposeEpilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.MethodsC3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the χ(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model.ResultsAn association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases.ConclusionFollowing the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014.

Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

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Association of BDNF gene polymorphism with asthma in polish children.

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Association of BDNF gene polymorphism with asthma in polish children.

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