Brain-derived Neurotrophic Factor (BDNF) Single Nucleotide Gene Polymorphism and Nerve Growth Factor as Risk Factors That Increase Severity of Allergic Rhinitis

Allergic diseases such as asthma, allergic rhinitis (AR) and atopic dermatitis affect more than 25% of the world population and are the leading cause of illness in children. The complex interplay between genetic, environmental and immunological risk factors results in the manifestation of allergic diseases . The pathological presentation of allergic disease involves the activation of both the innate and adaptive immune systems, resulting in a multifaceted response in specific target tissues such as the airways . This response results in the recruitment of inflammatory cells to target tissues and the production of specific IgE antibodies, cytokines and other inflammatory mediators [11], [12]. It is well established that allergic inflammation triggers neuronal dysfunction, which activates specific inflammatory mechanisms, potentially leading to structural changes in the diseased tissue . Neurotrophins are a family of structurally related proteins initially discovered to be involved in regulating neuronal development and now known to govern both peripheral and central nerve growth.

BDNF is a secretory protein belonging to the neurotrophin family and is involved in a range of neural processes during human development [19], [20]. In the early stages of development BDNF is essential for neurogenesis, survival and maturation of neuronal pathways. In the adult, alongside neurotransmitters, hormones and other neurotrophins, BDNF maintains synaptic plasticity, dendritic growth and the consolidation of long-term memory. The biological effect of BDNF is mediated via its binding to the trkB receptor. The activation of these receptors on eosinophils may be important in regulating the inflammatory cascade leading to allergic disease [15], [24]. Neurotrophin mediated activation of bronchial eosinophils might therefore play a role in the regulation of eosinophilic inflammation in allergic asthma .

The BDNF gene is located on chromosome 11p13 and is alternatively spliced resulting in several different transcripts [26]. Genetic polymorphisms in BDNF have been associated with allergic phenotypes such atopic dermatitis [27] and asthma [28], [29], [30], [31] in different populations. The functional polymorphism rs6265 (Val66Met) has been shown to regulate intracellular trafficking and affect the secretion of BDNF [32]. Nerve growth factor (NGF), a neurotrophin that is expressed in the glandular, nasal epithelium, and peripheral nerves in the nasal mucosa, has been shown to induce biochemical and structural changes in nerves that can lead to hyper-responsiveness [33], [34], [35] The biological effects of neurotrophins are mediated by binding either to the high-affinity tyrosine kinase (trk) receptors or to the low-affinity receptors known as pan-neurotrophin receptor p-75.

Study Overview

• Status: Recruiting
• Conditions: Allergic Rhinitis
• Intervention / Treatment: Diagnostic test: Genotyping.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: zeinab M Kadry, lecturer; Phone Number: 01225960747; Email: zainbmahmoud@med.sohag.edu.eg

Study Locations

• Egypt
  • Sohag, Egypt
    • Recruiting
    • Sohag University Hospital
    • Contact: Magdy M Amin, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

This study will be conducted on 50 patients 30 patients diagnosed as a clinical disease of AR according to the diagnostic criteria of AR based on, its Impact on Asthma criteria, the patient's history of allergic symptoms, and allergy test results using the ImmunoCAP system.

Description

Inclusion Criteria:

• The chronic AR patients on anti-allergic .

Exclusion Criteria:

• The chronic AR patients on anti-allergic therapy will be excluded.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BDNF gene single nucleotide polymorphism with Allergic rhinitis risk	will measure in blood	2 months
Nerve growth factor serum level	will measure in blood for the risk of Allergic rhinitis.	2 months
IL-1 serum level	will measure in blood for the risk of Allergic rhinitis.	2 months
C-reactive protein serum level	will measure in blood for the risk of Allergic rhinitis.	2 months

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T, Baena-Cagnani CE, Canonica GW, van Weel C, Agache I, Ait-Khaled N, Bachert C, Blaiss MS, Bonini S, Boulet LP, Bousquet PJ, Camargos P, Carlsen KH, Chen Y, Custovic A, Dahl R, Demoly P, Douagui H, Durham SR, van Wijk RG, Kalayci O, Kaliner MA, Kim YY, Kowalski ML, Kuna P, Le LT, Lemiere C, Li J, Lockey RF, Mavale-Manuel S, Meltzer EO, Mohammad Y, Mullol J, Naclerio R, O'Hehir RE, Ohta K, Ouedraogo S, Palkonen S, Papadopoulos N, Passalacqua G, Pawankar R, Popov TA, Rabe KF, Rosado-Pinto J, Scadding GK, Simons FE, Toskala E, Valovirta E, van Cauwenberge P, Wang DY, Wickman M, Yawn BP, Yorgancioglu A, Yusuf OM, Zar H, Annesi-Maesano I, Bateman ED, Ben Kheder A, Boakye DA, Bouchard J, Burney P, Busse WW, Chan-Yeung M, Chavannes NH, Chuchalin A, Dolen WK, Emuzyte R, Grouse L, Humbert M, Jackson C, Johnston SL, Keith PK, Kemp JP, Klossek JM, Larenas-Linnemann D, Lipworth B, Malo JL, Marshall GD, Naspitz C, Nekam K, Niggemann B, Nizankowska-Mogilnicka E, Okamoto Y, Orru MP, Potter P, Price D, Stoloff SW, Vandenplas O, Viegi G, Williams D; World Health Organization; GA(2)LEN; AllerGen. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008 Apr;63 Suppl 86:8-160. doi: 10.1111/j.1398-9995.2007.01620.x. No abstract available.
• Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007 Jan-Feb;28(1):3-9. doi: 10.2500/aap.2007.28.2934.
• Devereux G. The increase in the prevalence of asthma and allergy: food for thought. Nat Rev Immunol. 2006 Nov;6(11):869-74. doi: 10.1038/nri1958.
• Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008 Mar;8(3):169-82. doi: 10.1038/nri2257.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): August 10, 2023
• Study Completion (Estimated): August 10, 2023

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 15, 2023
• First Posted (Estimated): June 16, 2023

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: Soh-Med-23-04-09PD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No