Polimorfizmi u genu za beta-2 adrenergički receptor kod dece sa astmom u Srbiji i njihov klinički značaj

Abstract

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 detektovan 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.