Influence of the A3669G Glucocorticoid Receptor Gene Polymorphism on the Metabolic Profile of Pediatric Patients with Congenital Adrenal Hyperplasia
Open accessAbstract
Background . Pediatric CAH patients have an increased risk of cardiovascular disease, and it remains unknown if genetic predisposition is a contributing factor. Glucocorticoid receptor gene ( NR3C1 ) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of pediatric CAH patients. Methods . Forty-one patients (26SW/15SV) received glucocorticoid (GC) replacement therapy to achieve normal androgen levels. Obesity was defined by BMI ≥ 95 th percentile. NR3C1 alleles were genotyped, and association analyses with phenotype were done with Chi-square, t -test, and multivariate and regression analysis. Results . Obesity was observed in 31.7% of patients and was not correlated with GC doses and treatment duration. Z-score BMI was positively correlated with blood pressure, triglycerides, LDL-c levels, and HOMA-IR. NR3C1 polymorphisms, Bcl I and A3669G, were found in 23.1% and 9.7% of alleles, respectively. A3669G carriers presented higher LDL-c levels compared to wild-type subjects. Bcl I-carriers and noncarriers did not differ. Conclusion . Our results suggest that A3669G-polymorphism could be involved with a susceptibility to adverse lipid profile in pediatric CAH patients. This study provides new insight into the GR screening during CAH treatment, which could help to identify the subgroup of at-risk patients who would most benefit from preventive therapeutic action.
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Several genes were previously connected with fatty liver disease such as Nr3c1, Nr3c2, Zbtb16, Dnmt1, and Keap1, but most of the top genes had no connections with liver disease or NASH.
“Several genes were previously connected with fatty liver disease such as the glucocorticoid receptor Nr3c128,29, the mineralocorticoid receptor Nr3c230,31, the transcription factor Zbtb1632, the DNA methyltransferase Dnmt133, and the E3 ubiquitin ligase adaptor Keap134,35, but most of the top genes had no connections with liver disease or NASH.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [29]
The Results (§3.2) link an NR3C1 polymorphism to higher LDL cholesterol in pediatric patients with congenital adrenal hyperplasia. The cited paper does not address whether NR3C1 is connected with fatty liver disease or NASH; searches for fatty liver, hepatic steatosis, liver, and NASH found no passage establishing that connection. The other genes and the statement about most top genes are not attributed to this citation. (LLM, conf=0.77)
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Research works printed but not linked: 18
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- Authors
- Moreira, R. P. P., Gomes, L. G., Madureira, G., Mendonca, B. B., & Bachega, T. A. S. S.
- Affiliations
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Corresponding author
- Bachega, Tânia A. S. S.
- Venue
- International Journal of Endocrinology
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-6
- ISSN
- 1687-8337 (ISSN-L)
- 1687-8345
- PMC
- PMC4094695
- OpenAlex
- W2130633272
- Cited by
- 13
- References
- 31
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 2
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (09/54238-2, 09/54394-4, 308318/2012-9, 305743/2011-2)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (09/54238-2, 09/54394-4, 308318/2012-9, 305743/2011-2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- congenital adrenal hyperplasia, glucocorticoid receptor gene, NR3C1, BclI polymorphism, pediatric patients, obesity, lipid profile, LDL cholesterol, insulin resistance, cardiovascular risk, glucocorticoid replacement therapy, genetic susceptibility
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