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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Genetic: Genotyping by Real Time PCR

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 Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

• Study Contact: Name: Salma K Abdelmageed, demonstrator; Phone Number: 01091285241; Email: salma011101@med.sohag.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with epilepsy aged from 1 year to less than 15 years, in Pediatric department of Sohag University Hospital and healthy control children of matched age and sex

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• 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. doi: 10.1016/s0092-8674(03)00035-7.
• 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.
• 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, Moshe 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: BDNF in epileptic patients
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: Soh-Med-21-10-18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No