Polimorfizmi u genu za beta-2 adrenergički receptor kod dece sa astmom u Srbiji i njihov klinički značaj
ADRB2 gene polymorphisms and salbutamol responsiveness in serbian children with asthma
Докторанд
Jovičić, Nevena J.Ментор
Nestorović, BranimirЧланови комисије
Nikolić, AleksandraMilenković, Branislava
Simić, Dušica
Radojković, Dragica
Метаподаци
Приказ свих података о дисертацијиСажетак
agonisti beta-2 adrenergičnog receptora (ADRB2) su osnova terapije astme.
Beta-2 adrenergični receptor je protein koji je kodiran ADRB2 genom i varijante unutar
ovog gena mogu imati kao posledicu značajne modulacije terapijskog odgovora na
primenjen lek.
Metode: studija preseka je sprovedena u Univerzitetskoj dečjoj klinici u Beogradu u
periodu od oktobra 2016. do maja 2017. godine. U istraživanje je uključeno 54 dece sa
astmom uzrasta od 6 do 18 godina. Dijagnoza astme je postavljena u skladu sa GINA
smernicama. Ispitanici su u skladu sa GINA smernicama klasifikovani prema težini
bolesti u tri podgrupe: ispitanici sa blagom, umerenom i oni sa teškom astmom. Kod
svih ispitanika je uraĎena genotipizacija za polimorfizme ADRB2 +46A>G (Arg16Gli,
rs1042713) i +79C>G (Gln27Glu, rs1042714). Ispitana je povezanost ovih
polimorfizama sa težinom astme, kao i sa bronhodilatatornim odgovorom na inhalirani
salbutamol.
Rezultati: u ispitivanoj populaciji dece iz Srbije sa astmom, alel +46A je detek...tovan sa
učestalošću od 41,7%, a alel +79G je otkriven sa učestalošću od 23,1%. Ispitivanjem je
utvrĎeno da je alel +46G povezan sa boljim terapijskim odgovorom na inhalirani
salbutamol (p<0,05). Ovaj alel je povezan i sa blagim oblikom astme (p <0,05).
Zaključak: polimorfizam ADRB2 +46A>G može biti determinanta težine astme, kao i
bronhodilatatornog odgovora na salbutamol kod dece sa astmom u Srbiji. Nismo
pronašli povezanost polimorfizma +79C>G sa težinom astme i bronhodilatatornim
odgovorom na inhalirani salbutamol.
Rezultati ove studije mogu biti potencijalno korisni za personalizovani pristup lečenju
astme.
Background: Inhaled beta-2 adrenergic receptor (ADRB2) agonists are mainstay of
asthma therapy. The ADRB2 protein is encoded by the ADRB2 gene and variants
within this gene can have significant consequences for modulating the response to
asthma therapy.
Methods: This cross-sectional study was conducted at the University Children's
Hospital in Belgrade between October 2016 and May 2017. 54 children with asthma
aged 6 to 18 years are included in the study. The diagnosis of asthma is set in
accordance with GINA guidelines. Subjects are in accordance with GINA guidelines
classified according to the severity of the disease in three subgroups: subjects with mild,
moderate and those with severe asthma. In all subjects, genotyping for polymorphisms
ADRB2 + 46A>G (Arg16Gli, rs1042713) and + 79C>G (Gln27Glu, rs1042714) was
studied. The association of these polymorphisms with the severity of asthma and
bronchodilator response to inhaled salbutamol was studied.
Results: In the study population of ...Serbian asthmatic children, allel + 46A was detected
with a frequency of 41.7%, and allel + 79G was detected with a frequency of 23.1%.
The study found that allele + 46G was associated with a better response to inhaled
salbutamol (p <0.05). This allele is also associated with mild asthma (p <0.05).
Conclusions: Polymorphism of ADRB2 + 46G> A can be a determinant of asthma
severity and the bronchodilator response to salbutamol in children with asthma in
Serbia. We did not find the correlation of polymorphism + 79C> G with the severity of
asthma and the bronchodilator response to inhaled salbutamol. The results of this study
may be potentially useful for a personalized approach to the treatment of asthma.