Association between glucocorticosteroid receptor (NR3C1) gene polymorphism and bronchial asthma in children

Abstract

Background: There is a large variation in the magnitude of the response to asthma medications. Pharmacogenetics is responsible for a significant part of this variation. We aimed at studying the effect of the Glucocoricoid receptors NR3C1 BCLI single nucleotide polymorphism (SNP) on the susceptibility to bronchial asthma in children and to evaluate its effect on the response to inhaled corticosteroids (ICS). Method: Seventy five asthmatic children and a control group of 66 non asthmatic children were included in the study. The level of asthma symptom control and pulmonary function tests were measured initially and 3 months after treatment with inhaled corticosteroids. The genotypes were studied using PCR-RFLP method. Results: No statistically significant difference was found between asthmatic group and the control group as regard the studied genotype. Among asthmatic children, The CC genotype was statistically associated with controlled asthma symptoms 3 months after treatment and the GG genotype was associated with poor asthma symptom control. Also, FEV1% after 3 months of treatment was statistically lower in children with the GG genotype as compared to children with the CG and CC genotypes. Conclusion: glucocorticoid receptor NR3C1 SNP was not associated with asthma susceptibility in the studied group. However, the presence of the GG genotype was associated with decreased response to ICSs among asthmatic children as regards asthma symptom control and FEV1% response.

The effect of BclI polymorphism of NR3C1 gene on asthma phenotypes in Egyptian children

“…16 Also, in agreement with our study, Khaled et al 2020 noted among asthmatic children that the CC genotype was statistically associated with controlled asthma symptoms 3 months after treatment and the GG genotype was associated with poor asthma symptom control. 17 So, identification of genetic variation influencing treatment outcome in such heterogeneous disease (BA) with different endotypes and phenotypes might identify novel targets for biomarker-guided asthma treatment and preventative strategies. 18,19 In addition to this, the interaction with the environment that might play a major role in driving a predisposed genetic background toward severe and uncontrolled asthma phenotype, revealing the importance of the emerging Genome-wide interaction studies (GWIS) which assess the interaction between genome-wide genetic variance and environmental factors that might help in understanding this complex process.…”

Pharmacogenomic of asthma in children

“…Genetic variation in SPATA13 and its associated antisense RNA found to be associated with the BDR. 25 Long acting β2 agonists (LABA) for example: salmeterol and formoterol, act on ARβ2 which is the same as SABA, but works longer (8-12 h, compared to 3-5 h for SABA). LABAs are not prescribed as needed, but as primary maintenance treatment in combination with corticosteroids to avoid the increased risk of side effects associated with LABA monotherapy.…”

“…A rare variant in ADRβ2 has been associated with an increased risk of asthma-related hospitalization. 25…”

“…GLCCI1 has been identified as a genetic marker associated with improved lung function in corticosteroid use in children. 25…”

“…Leukotriene binds to leukotriene receptors on leukocytes and lung smooth muscle cells. 25 Pharmacogenomic effects in children are diverse, several pharmacogenomic studies of asthma treatment in various pediatric populations are described in TABLE 1. Children with atopic asthma with genotype AA when compared with patients with genotypes AG and GG had better treatment outcomes in response to anti asthmatic treatment with inhaled corticosteroids.…”