Effects of β2-adrenergic receptor polymorphisms on asthma severity and response to salbutamol in Egyptian children

Background: Several polymorphisms of the β2-adrenergic receptor (ADRB2) gene have been identified. There is mounting evidence that these polymorphisms are associated with significant variability in response to bronchodilator therapy and thus in severity and duration of asthmatic symptoms. Objectives: to assess the frequency of ADRB2 polymorphisms at codon 16 in Egyptian asthmatic children and to study the association of these polymorphisms with asthma severity and response to inhaled salbutamol. Methods: This case-control study was conducted at pulmonology unit, Zagazig University children’s hospital during the period from December 2010 to December 2011. One hundred children (50 asthmatics and 50 controls) were enrolled into the study. For all study population, detailed history taking, systematic physical examination, chest x-ray, pulmonary function testing and ADRB2 genotyping were performed. Results: There was a significant increase in frequencies of Arg/Gly and Gly/Gly genotypes among asthmatic children in comparison with healthy controls (OR = 7.9; CI: 0.94-67.4, P 0.05 and OR= 4.5; CI: 0.91-22.7, P 0.05 respectively). On the other hand, there was a lower frequency of Arg/Arg genotype in asthmatic children than that in healthy controls (OR = 0.14; CI: 0.04-0.55, P 0.05). Moreover, statistical analysis revealed association of Arg/Arg genotype with mild asthma (OR = 5.77; 95% CI: 1.55-21.5, P 0.05) and association of Gly/Gly genotype with moderate/severe asthma (OR=0.057; 95% CI: 0.006-0.516, P 0.05). However, no difference in distribution of Arg/Gly genotypes among mild and moderate/severe asthmatics (OR = 0.79; 95% CI: 0.156-3.99, P 0.05). Regarding bronchodilator responsiveness, Gly/Gly and Arg/Gly genotypes were associated with reduced response, while Arg/Arg genotype was associated with favorable response to nebulized salbutamol. Conclusion: Polymorphisms of ADRB2 at codon 16 may be a determinant of asthma severity and response to salbutamol in Egyptian asthmatic children. Further studies are needed to demonstrate effects of other polymorphisms of ADRB2 gene on these outcomes.