B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and response to treatment

Abstract

BackgroundAlterations of B2 adrenergic receptor (βAR) can modulate the severity of asthma and the response to treatment. Therefore, we aimed to evaluate βAR gene polymorphism at codons 16 and 27 and their effect on asthma severity and response to treatment in asthmatic children.MethodsCase-control study was conducted on 156 children; 104 of them had bronchial asthma and 52 were healthy children (control group). Subjects of the study underwent history taking, clinical examination, pulmonary function tests, serum IgE level assessment, and identification of βAR-16 A46G and βAR-27 C79G polymorphism using PCR-Restriction Fragment length polymorphisms (RFLP) test.ResultsThere was a higher frequency of Arg-Gly genotypes (odds ratio (OR)=6.57; confidence interval (CI): 2.42-18.81, P<0.001) and lower frequency of Arg-Arg (OR=4.7; CI: 2.05-10.95, P<0.001) among asthmatic children compared with that among controls at codon 16. The presence or absence of Gly16 or Glu27 either homozygous or heterozygous for both correlated with the grade of asthma severity. The presence of heterozygous Arg-Gly and Gln-Glu gives a better response to drug therapy than the presence of Gly-Gly and Glu-Glu genotypes at codons 16 and 27.ConclusionPolymorphism of βAR at codons 16 and 27 correlates with asthma severity and response to treatment in asthmatic children.

<p>Pharmacogenetics of Pediatric Asthma: Current Perspectives</p>

“…Between 2018 and 2019, the pharmacogenetic studies conducted in pediatric asthma have been mainly focused on therapeutic response to ICS and SABA albeit some of them have studied simultaneously the response to ICS and LABA/ LTRA. Altogether, eleven candidate-gene studies, [24][25][26][27][28][55][56][57][58][59] a meta-analysis of a candidate gene, 60 and six pharmacogenomic studies (one of them in adults but including replication in children) have been performed. 32,36,40,73,74,79 During this period, candidate-gene studies reported the association of genes previously described in pharmacogenetic studies of pediatric asthma with treatment response (ADRB2, GSDMB, FCER2, and VEGFA).…”

“…16,18,23 It encodes the β 2 adrenergic receptor, which is implicated in the bronchodilation process and is the biological target of β 2 adrenergic agonists. 19 In fact, in the reviewed period four candidate-gene studies have assessed the effect of the SNPs rs1042713 (arginine to glycine [Arg16Gly]) and rs1042714 (glutamic acid to glutamine [Glu27Gln]) on changes in lung function after SABA administration in European 24,25 and Egyptian 26,27 populations (Table 1). However, the results were not entirely consistent across studies.…”

“…On the other hand, none of these studies found an association of the SNP rs1042714 with SABA response. [24][25][26][27] Sordillo et al 28 conducted a longitudinal study in non-Hispanic white children (n=604) that were followed up 4-18 years. Four SNPs suggestively associated with SABA response by previous GWAS 21,29,30 (rs11252394, rs6988229, rs295137, and rs2626393) were studied for association with asthma treatment response and age interaction analyzing BDR after albuterol administration as outcome.…”

“…Several candidate-gene studies have been performed to evaluate the influence of genetic variants on treatment response to ICS (Table 2). 26,[54][55][56][57][58][59] Similarly to the response to SABA, the ADRB2 gene is one of the most extensively analyzed in pharmacogenetic studies of ICS. 16,18,23 In 2018, Sood et al 54 studied two SNPs (rs1042713 and rs1042714) from the ADRB2 gene in a European American and African American cohort (n=373) of children with asthma under ICS treatment.…”

“…Asthma individuals with CC genotype at the SNP rs1042714 had an increased risk of asthma exacerbation despite ICS treatment in comparison with heterozygous individuals (CG; p-value=0.04) and homozygous individuals (GG; p-value=0.013). 54 In the same year, Alghobashy et al 26 also evaluated these two SNPs in Egyptian children with asthma (n=52) treated with ICS in combination with LABA and assessed lung function measurement (FEV 1 and FEV 1 /FVC) as the primary outcome of treatment response. Worse treatment response to a combination of ICS plus LABA was reported for homozygous GG at rs1042713 (p-value<0.05) and homozygous GG at rs1042714 (p-value<0.05) individuals.…”