Association of platelet serotonin, plasma brain-derived neurotrophic factor (BDNF) and Val66Met BDNF gene polymorphism with asthma severity

doctoral thesis

• Title (croatian): Povezanost trombocitnoga serotonina, moždanoga neurotrofnoga čimbenika (BDNF) u plazmi te Val66Met polimorfizma gena BDNF sa stupnjem težine astme
• Author: Katherina Bernadette Sreter
• Mentor: Sanja Popović-Grle (mentor)
• Mentor: Dubravka Švob Štrac (komentor)
• Committee member: Jasenka Markeljević (predsjednik povjerenstva)
• Committee member: Miroslav Samaržija (član povjerenstva)
• Committee member: Nela Pivac (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-12-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Asthma is a common but complex chronic inflammatory disease of the respiratory airways.
Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are associated with
regulation of lung function and immune responses; however, their exact involvement in the
pathophysiology of asthma remains unclear. We investigated platelet 5-HT and plasma BDNF
concentrations, platelet monoamine oxidase B (MAO-B) activity, and the distribution of
genetic variants of BDNF rs6265 (Val66Met) and neurotrophic receptor tyrosine kinase 2
(NTRK2) rs1439050 polymorphisms in 120 asthma patients and 120 healthy subjects, and
evaluated their relationship with asthma severity and phenotype. Platelet 5-HT concentrations
were lower, whereas platelet MAO-B activity and plasma BDNF concentrations were higher
in asthma patients. No differences were observed in these parameters between subjects with
asthma subdivided according to asthma severity or phenotype. However, asthma patients with
aspirin sensitivity and aspirin-exacerbated respiratory disease had higher plasma BDNF
levels. The distribution of BDNF Val66Met and NTRK2 rs1439050 genetic variants showed
no differences between subjects with asthma and healthy individuals, or between patients with
different asthma severity and phenotype. The BDNF Val66Met polymorphism, but not
NTRK2 rs1439050 polymorphism, influenced plasma BDNF levels in healthy subjects only.
These results suggest that 5-HT and MAO-B in platelets as well as BDNF in plasma may
serve as potential peripheral biomarkers for asthma but not asthma severity.

Abstract (croatian)

Astma je česta ali kompleksna kronična upalna bolest dišnih putova. Serotonin (5-HT) i
moždani neurotrofni čimbenik (BDNF) su povezani s regulacijom funkcije pluća i
imunoloških odgovora; međutim, njihova točna uloga u patofiziologiji astme ostaje
nerazjašnjena. Istražili smo koncentracije trombocitnog 5-HT-a i BDNF-a u plazmi, aktivnost
trombocitne monoaminooksidaze B (MAO-B), i raspodjelu genskih varijanti BDNF rs6265
(Val66Met) polimorfizma i NTRK2 (gen za neurotrofni receptor tirozin kinaza 2) rs1439050
polimorfizma u 120 pacijenata s astmom i 120 zdravih osoba, te istražili njihovu povezanost
sa stupnjem težine i fenotipom astme. Koncentracije trombocitnog 5-HT-a bile su snižene,
dok su aktivnost trombocitne MAO-B i koncentracije BDNF-a u plazmi bile povišene u
pacijenata s astmom. Nisu opažene razlike u ovim parametrima između osoba oboljelih od
astme podijeljenih prema težini bolesti ili fenotipu. Međutim, pacijenti s aspirin-osjetljivom
astmom i aspirin-pogoršanom respiratornom bolešću imali su povišene razine BDNF-a u
plazmi. Raspodjela genskih varijanti BDNF Val66Met i NTRK2 rs1439050 polimorfizama
nije pokazala razliku niti između pacijenata s astmom i zdravih osoba niti između oboljelih
različitih stupnjeva težine i fenotipova astme. BDNF Val66Met polimorfizam, ali ne i NTRK2
rs1439050 polimorfizam, utjecao je na razine BDNF-a u plazmi samo zdravih ispitanika. Ovi
rezultati ukazuju da 5-HT i MAO-B u trombocitima, te BDNF u plazmi mogu poslužiti kao
potencijalni periferni biomarkeri za astmu, ali ne i za težinu astme.

• Keywords: asthma; plasma BDNF concentrations; platelet 5-HT levels; platelet MAO-B activity; BDNF and NTRK2 polymorphisms; severity; phenotype
• Keywords (croatian): astma; koncentracija BDNF-a u plazmi; razina trombocitnog 5-HT-a; trombocitna MAO-B aktivnost; polimorfizmi BDNF i NTRK2; težina bolesti; fenotip
• Language: english
• URN:NBN: urn:nbn:hr:105:643274
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 163 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-01-30 12:13:54