FCER2 T2206C variant associated with FENO levels in asthmatic children using inhaled corticosteroids: The PACMAN study

Abstract

BackgroundThe FCER2 gene, via encoding of the CD23 receptor, plays an important role in the regulation of IgE responses. A genetic variant of the FCER2 gene (T2206C) was previously shown to be associated with IgE levels in asthmatic children. IgE sensitization has also been linked to increased levels of fractional exhaled nitric oxide (FENO).ObjectiveTo investigate whether the FCER2 T2206C variant influences FENO levels in asthmatic children with a reported use of inhaled corticosteroids (ICS).MethodsThis cross‐sectional study involved 593 asthmatic children with a reported use of ICS, availability of FENO measurements and genotyping data on the FCER2 T2206C variant (rs28364072). An additive genetic model was assumed, and the association between the FCER2 T2206C variant and the log‐transformed (ln) FENO levels was evaluated using linear regression analysis, adjusted for age, sex, adapted British Thoracic Society (BTS) treatment steps and atopy.ResultsThe mean age of the population was 9.1 ± 2.2 years, and the median of FENO levels was 13.0 ppb with an interquartile range (IQR) of (8.0‐27.5 ppb). The minor allele (G) frequency of rs28364072 was 29.6%, and each extra copy of the G allele was significantly associated with a lower level of the geometric mean of FENO (log scale, β = −0.12, 95% CI: −0.23, −0.02).Conclusion and Clinical RelevanceOur results showed that the FCER2 T2206C variant was significantly associated with lower FENO levels in carriers of the G allele. Nevertheless, this SNP contributed little to the variability in FENO levels in this patient population. Our findings contribute to the present knowledge on FENO in asthmatic children; however, future replication studies are required to establish the role of this gene in relation to FENO.

<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).…”

“…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.…”

“…Nevertheless, when stratified analyses based on asthma control status were performed, this effect was not observed in patients with partially controlled and uncontrolled asthma. 57 Some studies have evaluated the effect of genetic variants not only on ICS response but also on LTRA. Dragicevic et al 58 conducted a randomized longitudinal study in European children with asthma (n=127) who were treated with ICS or LTRA and evaluated the effect of two MMP9 gene SNPs on treatment response.…”

Asthma management and impact on COVID‐19 outcomes

“…One area of intense current research interest in asthma is pharmacogenomics, that is evaluating genetic variants that might explain the response to treatment and lead to targeted asthma treatments based on genotype 2 . Karimi et al previously reported in this journal that a genetic variant in the low‐affinity IgE receptor may influence airway inflammation as measured by exhaled nitric oxide 3 . In this issue, the same group report work from the multiethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium of 10 separate studies 4 .…”

Developments allergy in 2019 through the eyes of Clinical and Experimental Allergy, Part II clinical allergy

“…In a study focused on polymorphism of a gene encoding the low affinity IgE receptor, CD23 (FCER2) was found to be associated with reduced FeNO levels in well controlled asthmatic children using ICS for asthma management. 61 The polymorphism in FCER2 was considered to lead to reduced expression of CD23 resulting in lower levels of IgE and reduced FeNO. However, the findings might be confounded by the direct effects of ICS on lowering FeNO, though in this study, ICS dosage was not correlated with FeNO.…”