ESPEYB16 8. Adrenals New Genes (2 abstracts)
8.11. Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study
Hawcutt DB , Francis B , Carr DF , Jorgensen AL , Yin P , Wallin N , O’Hara N , Zhang EJ , Bloch KM , Ganguli A , Thompson B , McEvoy L , Peak M , Crawford AA , Walker BR , Blair JC , Couriel J , Smyth RL & Pirmohamed M
Department of Women’s and Children’s Health, University of Liverpool, Liverpool, UK; Wolfson Centre for Personalised Medicine, Medical Research Council Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
To read the full abstract: Lancet Respir Med. 2018; 6(6): 442–450.
Inhaled corticosteroids (ICS) are widely used by patients with asthma or chronic obstructive pulmonary disease (COPD). Although ICS are generally well tolerated and have fewer systemic adverse effects than oral corticosteroids, some patients develop systemic adverse effects. Adrenal suppression is a clinically important adverse effect, particularly in children with asthma, but its detection is challenging because presentation can range from asymptomatic biochemical changes to non-specific lethargy to florid adrenal crisis and death. The aim of the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) study was to undertake the first pharmacogenomic assessment of corticosteroid-induced adrenal suppression among children with asthma using ICS.
The authors found common variants in the platelet-derived growth factor D (PDGFD) gene associated with adrenal suppression. These findings were validated in separate groups of children with asthma (the PASS study) and adults with COPD (the Pharmacogenomics of Adrenal Suppression in COPD [PASIC] study) - the rs591118 variant showed genome-wide significance in both groups. The validation in the adult cohort is especially remarkable since these patients had a different chronic disease, had multiple comorbidities, and were on multiple medications, further reinforcing this novel finding. Heterogeneity between studies was higher for COPD (44%) than for asthma (0%), which could reflect greater heterogeneity in COPD.
These data support the idea of a genetic basis for inter-individual variation in susceptibility to corticosteroid-induced adrenal suppression. The findings offer the potential to develop translational pathways to prevent corticosteroid-induced adrenal suppression, thereby improving the benefit–risk ratio of this important therapy.
Volume 16
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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