1 BACKGROUND
It has been shown that 16.3 % of asthmatic children treated with
inhaled corticosteroids (ICS) and nasal steroids (NS) in Cape Town,
South Africa, can develop hypothalamic-pituitary-adrenal axis
suppression (HPAS) when assessed with the metyrapone(MTP)
test.1-2 If partial forms of suppression are included,
even two-thirds of children may be affected. A higher body mass index
(BMI) was found to be protective against HPAS. Unfortunately suitable
screening tests for HPAS are not available.3-4The only
viable alternative thus would be to identify gene variants, which would
help to predict which children are either prone or resistant to
developing HPAS.
In Greek asthmatic childrenon inhaled corticosteroids,homozygotes for
the single nucleotide polymorphisms (SNPs) rs242941 (TT) and rs1876828
(AA) of the corticotrophin-releasing hormone receptor 1 (CRHR1) gene
were associated with lower stimulated cortisol (F) levels when tested
with the low dose adrenocorticotropin (ACTH) stimulation test
(0.5µg/1.73m2). Heterozygotes (GC) for rs41423247
(Bcl l restriction length polymorphism) of the glucocorticoid
receptor (NR3C1) gene,on the other hand,were found to have higher basal
F levels.5 In the quest for universally applicable
predictors of HPAS in asthmatic children on corticosteroids, the
findings of the Greek study needed to be confirmed by a study, utilizing
the gold standard metyrapone test, to determine whether the SNPs
rs242941 and rs1876828 of the CRHR1, and rs41423247 of the NR3C1 gene
are associated with HPAS in asthmatic school children on
corticosteroids.