Association of Brain Derived Neurotrophic Factor (BDNF) rs6265 Gene Polymorphism With Susceptibility to Epilepsy
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Group I patients with epilepsy |
Genetic: Genotyping by Real Time PCR
3 mL of blood will be withdrawn by venipuncture in EDTA tube.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).
|
| Group II apparently healthy controls with no chronic illness of matched age and sex |
Genetic: Genotyping by Real Time PCR
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).
|
Outcome Measures
Primary Outcome Measures
- Iinvestigate the possible association between BDNF rs6265 polymorphism and epilepsy susceptibility in Egyptian patients [within 3 days after collection of samples]
Genotyping assay of ( BDNF ) rs6265 gene polymorphism by the Real- time polymerase chain reaction.
Secondary Outcome Measures
- Assess the utility of serum BDNF concentration as a diagnostic tool for Epilepsy and evaluate its relationship with disease severity [within 3 days after collection of samples]
Measurement BDNF level in serum by Sandwich enzyme linked immunosorbant assay kit
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Sohag University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004 May 5;24(18):4401-11.
- Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-69.
- Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. Epub 2014 Apr 14. Review.
- Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539. Review.
- Soh-Med-21-10-18