Marker Predicts Corticosteroid-Induced Adrenal Suppression in Asthma Patients

A genetic variation in the PDGFD gene locus is associated with increased risk of adrenal suppression in patients treated with corticosteroids for asthma and chronic obstructive pulmonary disease (COPD), according to the results of a recent study.

Adrenal suppression is a serious adverse effect associated with corticosteroid therapy. To explore whether any genetic variants could affect susceptibility to corticosteroid-induced adrenal suppression, researchers enrolled children with asthma in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) study, which included 2 validation cohorts: children with asthma (PASS study) and adults with COPD recruited from 2 UK centers for the Pharmacogenomics of Adrenal Suppression in COPD (PASIC) study.

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All participants underwent low-dose short synacthen testing. Adrenal suppression was defined as peak cortisol less than 350 nmol/L in children and less than 500 nmol/L in adults. A case-control genome-wide association study was conducted with the control subset augmented by participants from Wellcome Trust Case Control Consortium 2 (WTCCC2).

Overall, adrenal suppression was observed in 35 children (7%) in the discovery cohort and 6 children (7%) and 17 adults (22%) in the validation cohorts. In the discovery cohort, 40 single nucleotide polymorphisms (SNPs) were found to be associated with adrenal suppression, including an intronic SNP within the PDGFD gene locus (rs591118). These findings were validated for both the pediatric asthma and adult COPD cohorts. Meta-analysis of the pediatric cohorts (discovery and validation) and all 3 cohorts showed genome-wide significance of rs591118.

“Our finding is highly novel, and its importance is emphasized by its validation in a multimorbid adult population with COPD,” the researchers concluded.

—Michael Potts

Reference:

Hawcutt DB, Francis B, Carr DF ,et al. Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study. Lancet Respir Med. 2018;6(6)442-450.