Association of Brain Derived Neurotrophic Factor (BDNF) rs6265 Gene Polymorphism With Susceptibility to Epilepsy

Study Overview
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Brief Summary
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Epilepsy is a common neurological condition that affects people of all ages.Recent studies found that epilepsy is associated with several chromosomal regions, where mutations in these regions cause neurological dysfunction. BDNF which is the most ample neurotropic factor in the CNS, has survival and growth promoting roles in a variety of neurons. It has been shown to promote excitatory (glutamatergic) synapses while weakening inhibitory (GABAergic) ones. A nonsynonymous G to A single-nucleotide polymorphism (SNP) exists at position 196 of exon 2 (rs6265), which results in valine (val) to methionine (met) substitution. This polymorphism affects intracellular packaging of pro-BDNF, its axonal transport and in turn, activity-dependent secretion of BDNF at the synapse.

Detailed Description
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Epilepsy was defined as the separate occurrence of two or more unprovoked seizures, manifested by involuntary motor, sensory, or autonomic, alone or in combination, and not diagnosed as neonatal or febrile seizures. Despite extensive studies, the molecular causes of the disease are not yet discovered completely. A functional imbalance between excitatory (transmitted by glutamate) and inhibitory signals (transmitted by γ-amino butyric acid or GABA) in neural cells has been regarded as a putative contributing factor in epilepsy. The brain-derived neurotropic factor (BDNF) encodes a small dimeric protein which is the most ample neurotropic factor in the CNS.It has been shown to promote excitatory (glutamatergic) synapses while weakening inhibitory (GABAergic) ones.Any interference with the BDNF signaling pathway may negatively affect downstream neuronal functions and cause neuronal diseases. A nonsynonymous G to A single-nucleotide polymorphism (SNP) exists at position 196 of exon 2 (rs6265), which results in valine (val) to methionine (met) substitution at codon 66 (val66met), changing the 5' proregion of the human BDNF protein. This polymorphism affects intracellular packaging of pro-BDNF, its axonal transport and in turn, activity-dependent secretion of BDNF at the synapse

Official Title
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Association of Brain Derived Neurotrophic Factor (BDNF) rs6265 Gene Polymorphism With Susceptibility to Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Genetic: Genotyping by Real Time PCR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Epileptic patients aged more than 1 year and less than 15 year who recently had seizures over a period of one year Exclusion Criteria: Patients > 15 years old or less than 1 year. Patients that have epilepsy as a result of head injuries, brain tumors , exposure to low oxygen during birth or infections such as meningitis or encephalitis . Patients that have no sufficient medical records or unreliable seizure frequency, patients with developmental disorders such as Autism and Neurofibromatosis

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group I<br>patients with epilepsy | Genetic: Genotyping by Real Time PCR<br>* 3 mL of blood will be withdrawn by venipuncture in EDTA tube. DNA extraction will be done after centrifugation and used for genotyping assay of ( BDNF ) gene with the Real- time polymerase chain reaction. BDNF level in serum will also be analyzed by Sandwich enzyme linked immunosorbant assay kit ( ELISA).<br>|
| Group II<br>apparently healthy controls with no chronic illness of matched age and sex | Genetic: Genotyping by Real Time PCR<br>* 3 mL of blood will be withdrawn by venipuncture in EDTA tube. DNA extraction will be done after centrifugation and used for genotyping assay of ( BDNF ) gene with the Real- time polymerase chain reaction. BDNF level in serum will also be analyzed by Sandwich enzyme linked immunosorbant assay kit ( ELISA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iinvestigate the possible association between BDNF rs6265 polymorphism and epilepsy susceptibility in Egyptian patients | Genotyping assay of ( BDNF ) rs6265 gene polymorphism by the Real- time polymerase chain reaction. | within 3 days after collection of samples | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the utility of serum BDNF concentration as a diagnostic tool for Epilepsy and evaluate its relationship with disease severity | Measurement BDNF level in serum by Sandwich enzyme linked immunosorbant assay kit | within 3 days after collection of samples | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BDNF in epileptic patients