Pharmacogenetics of inhaled corticosteroids and exacerbation risk in adults with asthma.

View Abstract

BACKGROUND

Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses.

OBJECTIVE

We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment.

METHODS

We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population-based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome.

RESULTS

Rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR=6.11, P<0.005). In contrast, rs1134481 T allele within TBXT (Chromosome 6, member of a family associated with embryonic lung development) showed better response with ICS. Rs37973 G allele (GLCCI1) showed a significantly poorer response on ICS within the discovery cohort which was also significant but in the opposite direction in the replication cohort.

CONCLUSION

Rs242941 in CRHR1 was associated with poor ICS response. Conversely, TBXT variants were associated with improved ICS response. These associations may reveal specific endotypes, potentially allowing prediction of exacerbation risk and ICS response.

Investigators
Abbreviation
Clin Exp Allergy
Publication Date
2021-01-11
Pubmed ID
33428814
Medium
Print-Electronic
Full Title
Pharmacogenetics of inhaled corticosteroids and exacerbation risk in adults with asthma.
Authors
Edris A, de Roos EW, McGeachie MJ, Verhamme KMC, Brusselle GG, Tantisira KG, Iribarren C, Lu M, Wu AC, Stricker BH, Lahousse L