Background: Several polymorphisms of the ?2-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. |