Anthropometrics and Metabolic Syndrome in Relation to Glucocorticoid Receptor Polymorphisms in Corticosteroid Users
Open accessAbstract
Introduction: Corticosteroids are widely prescribed and their use has been linked to adverse cardiometabolic outcomes. A pivotal role in the action of corticosteroids is reserved for the glucocorticoid receptor (GR). Here, we assessed the relationship of glucocorticoid sensitivity-altering GR polymorphisms with anthropometrics and metabolic syndrome (MetS) in corticosteroid users. Methods: In this population-based cohort study (Lifelines), we genotyped 10,621 adult participants for GR hypersensitive (1/2 copies Bcl I and/or N363S) and GR resistant (1/2 copies ER22/23EK and/or 9β) variants. We assessed the relationship between functional GR polymorphisms with BMI, waist circumference (WC), and MetS in users of corticosteroids. Results: Overall corticosteroid use was associated with a significantly higher BMI and WC in GR wild-type (WT) users (BMI, +0.63 kg/m 2 [0.09–1.16], p = 0.022; WC, +2.03 cm [0.61–3.44], p = 0.005) and GR hypersensitive (BMI, +0.66 kg/m 2 [95% CI, 0.31–1.01]; WC, +2.06 cm [1.13–2.98], both p < 0.001) but not in GR resistant users. Significantly higher WC in GR resistant carriers was observed only for inhaled corticosteroid users. With respect to MetS, again only GR WT users (odds ratio [OR] 1.44 [1.07–1.94], p = 0.017) and GR hypersensitives (OR 1.23 [95% CI, 1.00–1.50], p = 0.046) were more likely to have MetS; even more pronounced in only inhaled corticosteroid users (GR WT users, OR 1.64 [1.06–2.55], p = 0.027; GR hypersensitive users, OR 1.43 [1.08–1.91], p = 0.013). Conclusions: Polymorphisms associated with increased GR sensitivity and WT GR are related to increased BMI, WC, and an increased MetS presence in corticosteroid users, especially of the inhaled types, when compared to nonusers. The adverse effects of corticosteroid use are less pronounced in users harboring GR resistant polymorphisms.
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Adverse effects were less pronounced in corticosteroid users harboring gene polymorphisms associated with glucocorticoid receptor resistance.
“Interestingly, the adverse effects were less pronounced in corticosteroid users harboring gene polymorphisms, which are associated with glucocorticoid receptor resistance (39).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [39]
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Kachkovska, V. (2023) · Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego · doi:10.36740/merkur202304115
- Authors
- Savas, M., Wester, V. L., van der Voorn, B., Iyer, A. M., Koper, J. W., van den Akker, E. L. T., & van Rossum, E. F. C.
- Affiliations
- Erasmus MC (NL)
- ORCID
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2020-12-11
- Volume
- 111
- Issue
- 11
- Pages
- 1121-1129
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W3112052265
- Cited by
- 13
- References
- 37
- Citations by year
- 2025: 3 · 2023: 6 · 2022: 4
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroendocrinology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- ZonMw (91716453)
- Ministerie van Volksgezondheid, Welzijn en Sport
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91716453)
- Universitair Medisch Centrum Groningen
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- glucocorticoid receptor, corticosteroid use, metabolic syndrome, anthropometry, body mass index, waist circumference, glucocorticoid hypersensitivity, glucocorticoid resistance, inhaled corticosteroids, genetic susceptibility, cardiometabolic risk
- MeSH terms
- Adrenal Cortex Hormones, Adult, Aged, Anthropometry, Female, Humans, Male, Middle Aged, Polymorphism, Genetic, Receptors, Glucocorticoid, Cohort Studies, Body Mass Index, Metabolic Syndrome, Waist Circumference, Genome-Wide Association Study
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