Značaj genetskih i faktora sredine u nastanku idiopatskih bronhiektazija kod dece
Significance of genetic and environmental factors in childhood idiopathic bronchiectasis
Author
Milošević, Katarina J.Mentor
Nestorović, BranimirCommittee members
Nikolić, Aleksandra
Škodrić-Trifunović, Vesna

Nagorni Obradović, Ljudmila

Radojković, Dragica

Metadata
Show full item recordAbstract
Cilj: U ovoj studiji ispitivan je uticaj mutacija u genima za regulator transmembranske
provodljivosti u cističnoj fibrozi (CFTR) i neutrofilnu elastazu (ELANE) i uticaj faktora
sredine (sekundarno pušenje, uslovi stanovanja i socioekonomski status) na pojavu ne CFbronhiektazija
kod dece.
Metodologija: Analizom je obuhvaćeno 48 ispitanika, starosti od 5 do 17 godina, kod kojih
je dijagnoza idiopatskih bronhiektazija ustanovljena na osnovu skenera visoke rezolucije
pluća. Kod svih pacijenata su primenjeni antibiotici, anti-inflamatorni lekovi, ekspektoransi
i posturalna drenaža. Odgovor na terapiju praćen je promenom izdahnutog azot monoksida
(NO) pre i posle terapije. Za analizu gena CFTR i ELANE korišćena je DNK izolovana iz
uzoraka venske krvi, a analiza je vršena metodologijom zasnovanom na PCR (polymerase
chain reaction) tehnici. Prisustvo promena u odabranim segmentima gena CFTR i ELANE
vršeno je direktnim sekvenciranjem DNK.
Rezultati: Mutacija c.1521_1523delCTT (F508del) je okri...vena sa učestalošću od 1.0%,
Zastupljenost genotipova koji sadrže varijantu c.1210-12T[5] (IVS8-5T) je viša nego u
opštoj populaciji (10.4% vs. 5.0%, P = 0.0302). Postoji statistički značajna razlika u
vrednosti inicijalnog NO između dece sa niskom/srednjom i visokom ELANE
promotorskom aktivnošću (t=2,906;p=0,006). Deca sa visokom aktivnošću imaju značajno
višu incijalnu vrednost NO. Takođe postoji statistički značajna razlika u vrednosti promene
NO između između dece sa niskom/srednjom i visokom promotorskom aktivnošću ELANE
gena (t=3,329;p=0,002). Deca sa visokom aktivnošću imaju značajno veću promenu NO.
Utvrđeno je i da postoji statistički značajna povezanost promene NO i promotorske
aktivnosti ELANE gena (r=0,350;p=0,015)...
Aim: This study has investigated a potential role of common Cystic Fibrosis Transmembrane
Conductance Regulator (CFTR) and neutrophil elastase (ELANE) gene variants and the impact of
environmental factors (secondary smoking, living conditions and socioeconomic status) in the
etiology of non-cystic fibrosis bronchiectasis in children.
Methods: The study included 48 children between 5 and 17 years old who were diagnosed
with idiopathic bronchiectasis based on high-resolution computed tomography of the
thorax. In all patients therapy included administration of antibiotics, anti-inflammatory
drugs, expectorants, and postural drainage. Response to therapy was evaluated by the
change in NO levels before and after administration of therapy. The CFTR and ELANE gene
analysis was performed on genomic DNA extracted from peripheral blood samples of
patients by polymerase chain reaction (PCR) method. The CFTR and ELANE promoter
region variants were analyzed by PCR-direct DNA sequencing.
Results: Mu...tation c.1521_1523delCTT (F508del) was detected with an allelic frequency of
1.0%, and c.224G > A (R75Q) variant. Carriers of c.1210-12T[5] (IVS8-5T) allele were
significantly more common than in the general population (10.4% vs. 5.0%, P = 0.0302).
Subjects in the group with high-activity genotype had higher initial FeNO levels and this
difference was statistically significant (t = 2.906; p = 0.006). The difference between FeNO
levels before and after therapy was also statistically significantly higher in children with
high-activity genotype (t = 3.329; p = 0.002). Statistically significant correlation was
observed between the change in FeNO levels and ELANE genotypes (r = 0.350; p = 0.015)...