Akurugu Wisdom Alemya, Van Heerden Carel Jacobus, Mulder Nicola, Zöllner Ekkehard Werner
Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa.
Pediatr Allergy Immunol. 2021 Feb;32(2):273-279. doi: 10.1111/pai.13379. Epub 2020 Oct 13.
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) gene were associated with lower stimulated cortisol (F) levels, whereas rs41423247 of the glucocorticoid receptor (NR3C1) gene was associated with higher basal F levels. The objective of the current study was to confirm whether these three SNPs are associated with HPAS in asthmatic children.
DNA was extracted from saliva obtained from 95 asthmatic children, who had previously undergone basal F and metyrapone testing. Thirty-six children were classified as suppressed. Non-suppressed children were subclassified according to their post-metyrapone adrenocorticotropin (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.
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 = .021). √PMTP ACTH was associated with CC (effect size = 10.85, P = .005) and GC genotypes (effect size = 4.06, P = .023). The C allele is inherited as a dominant trait (effect size = -1.31 (95% CI -2.39--0.33; P = .012). In the high ACTH response group, both genotypes affected the PMTP ACTH (effect sizes 1.41 and 15.46; P-values .023 and <2 × 10 for GC and CC, respectively).
The C allele of rs41423247 was found to be protective against HPAS. CC genotype is associated with the highest PMTP ACTH response.
使用皮质类固醇的哮喘儿童可能会出现下丘脑 - 垂体 - 肾上腺轴抑制（HPAS）。促肾上腺皮质激素释放激素受体1（CRHR1）基因的单核苷酸多态性（SNP）rs242941和rs1876828与较低的刺激皮质醇（F）水平相关，而糖皮质激素受体（NR3C1）基因的rs41423247与较高的基础F水平相关。本研究的目的是确认这三个SNP是否与哮喘儿童的HPAS相关。
从95名曾接受基础F和甲吡酮测试的哮喘儿童的唾液中提取DNA。36名儿童被归类为受抑制。未受抑制的儿童根据其甲吡酮后促肾上腺皮质激素（PMTP ACTH）水平分为中等（106 - 319 pg/mL）和高（>319 pg/mL）ACTH反应组。采用TaqMan聚合酶链反应测定法。
仅rs41423247与HPAS呈负相关（OR = 0.27 [95% CI 0.06 - 0.90]）。其GC基因型与HPAS呈负相关（对数优势 = -1.28，P = 0.021）。√PMTP ACTH与CC（效应大小 = 10.85，P = 0.005）和GC基因型（效应大小 = 4.06，P = 0.023）相关。C等位基因作为显性性状遗传（效应大小 = -1.31（95% CI -2.39--0.33；P = 0.012）。在高ACTH反应组中，两种基因型均影响PMTP ACTH（GC和CC的效应大小分别为1.41和15.46；P值分别为0.023和<2×10）。
发现rs41423247的C等位基因对HPAS有保护作用。CC基因型与最高的PMTP ACTH反应相关。
