Author responsible for correspondence
EW Zöllner
Faculty of Health Sciences
Department of Paediatrics and Child Health
Stellenbosch University
PO Box 241
Cape Town
8000
South Africa
Word count : 2480
Word count abstract: 250
Title character count : 99
No of tables: 5
No of figures: 1
Conflict of interest
WAA, CJVH, NM & EWZ have nothing to disclose.
Financial support
This study was supported by grants from the National Research Foundation
and the South African Thoracic Society.
Abstract and keywords
Background: Asthmatic children on corticosteroids can develop
hypothalamic-pituitary-adrenal axis suppression (HPAS). Single
nucleotide polymorphisms (SNPs) rs242941 and rs1876828 of the
corticotrophin-releasing hormone receptor 1 (CRHR1) genewere associated
with lower stimulated cortisol (F) levels,whereas rs41423247 of the
glucocorticoid receptor (NR3C1) genewas associated with higher basal F
levels. The objective of the current study was to confirmwhether these
three SNPs are associated with HPAS in asthmatic children.
Methods: DNA was extracted from saliva obtained from
95asthmatic children, who had previously undergone basal F and
metyrapone testing. Thirty-six children were classified as suppressed.
Non-suppressed children were sub-classified according to their
post-metyrapone ACTH (PMTP ACTH)level into a middle (106-319 pg/ml) and
a high (>319 pg/ml) ACTH response group.
TaqMan®polymerase chain reaction assays were utilized.
Results: Only rs41423247 was inversely associated with HPAS (OR
= 0.27 [95% CI 0.06-0.90]). Its GC genotype was inversely
associated with HPAS (log odds = - 1.28, p = 0.021). √PMTP ACTH was
associated with CC (effect size = 10.85, p = 0.005) and GC genotypes
(effect size = 4.06, p = 0.023). The C allele is inherited as a dominant
trait (effect size = -1.31 (95% CI -2.39 – -0.33; p = 0.012). In the
high ACTH response group, both genotypes affected the PMTP ACTH (effect
sizes 1.41 and 15.46; p-values 0.023 and <
2x10-26 for GC and CC respectively).
Conclusions: TheC allele of rs41423247was found to be
protective against HPAS. CC genotype is associated with the highest
PMTPACTH response.
Key words: Asthma, hypothalamus, pituitary, adrenal,
polymorphism, receptors, glucocorticoids, steroids/adverse events,
adrenal insufficiency, pituitary-adrenal-function tests
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