Značaj genetskih i faktora sredine u nastanku idiopatskih bronhiektazija kod dece

Abstract

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 okrivena 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: Mutation 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)...