The effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia
Open accessAbstract
The 21‐hydroxylase deficiency ( 21OHD ) is caused by CYP21A2 mutations resulting in severe or moderate enzymatic impairments. 21OHD females carrying similar genotypes present different degrees of external genitalia virilization, suggesting the influence of other genetic factors. Single nucleotide variants ( SNVs ) in the CYP3A7 gene and in its transcription factors, related to fetal 19‐carbon steroid metabolism, could modulate the genital phenotype. To evaluate the influence of the 21OHD genotypes and the CYP3A7 , PXR and CAR SNVs on the genital phenotype in 21OHD females. Prader scores were evaluated in 183 patients. The CYP3A7 , PXR and CAR SNVs were screened and the 21OHD genotypes were classified according to their severity: severe and moderate groups. Patients with severe genotype showed higher degree of genital virilization (Prader median III , IQR III‐IV ) than those with moderate genotype ( III , IQR II‐III ) (p < 0.001). However, a great overlap was observed between genotype groups. Among all the SNVs tested, only the CAR rs2307424 variant correlated with Prader scores ( r 2 = 0.253; p = 0.023). The CYP21A2 genotypes influence the severity of genital virilization in 21OHD females. We also suggest that the CAR variant, which results in a poor metabolizer phenotype, could account for a higher degree of external genitalia virilization.
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Apart from CAH genes, other genes may modify steroid action, salt balance or androgen sensitivity and affect phenotype.
“Apart from CAH genes, other genes may modify steroid action, salt balance or androgen sensitivity and affect phenotype.136,137,138”
From Congenital adrenal hyperplasia (2017) · cites this paper as [137]
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- Authors
- Kaupert, L., Lemos‐Marini, S., De Mello, M., Moreira, R., Brito, V., Jorge, A., Longui, C., Guerra, G., Mendonca, B., & Bachega, T.
- Affiliations
- Laboratório de Hormônios e Genética Molecular‐ LIM/42 Unidade de Endocrinologia do Desenvolvimento, Disciplina de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo São Paulo Brazil
- Unidade de Endocrinologia Pediátrica Departamento de Pediatria, Faculdade de Ciências Médicas da Universidade Estadual de Campinas Campinas São Paulo Brazil
- Centro de Biologia Molecular e Engenharia Genética Universidade Estadual de Campinas Campinas São Paulo Brazil
- Universidade de São Paulo (BR)
- Unidade de Endocrinologia Pediátrica Departamento de Pediatria, Irmandade da Santa Casa de Misericórdia de São Paulo São Paulo Brazil
- Venue
- Clinical Genetics
- Publisher
- Wiley
- Published
- 2012-10-08
- Volume
- 84
- Issue
- 5
- Pages
- 482-488
- ISSN
- 0009-9163 (ISSN-L)
- 1399-0004
- OpenAlex
- W1543673058
- Cited by
- 17
- References
- 39
- Citations by year
- 2024: 1 · 2023: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2017: 4 · 2016: 1 · 2013: 2
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Clinical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- 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, 21-hydroxylase deficiency, CYP21A2 mutations, CYP3A7, pregnane X receptor, single nucleotide variants, genotype severity
- MeSH terms
- Pregnane X Receptor, Constitutive Androstane Receptor, Adrenal Hyperplasia, Congenital, Alleles, Aryl Hydrocarbon Hydroxylases, Child, Child, Preschool, Female, Gene Frequency, Genitalia, Genotype, Humans, Infant, Newborn, Receptors, Steroid, Retrospective Studies, Severity of Illness Index, Steroid 21-Hydroxylase, Virilism, Receptors, Cytoplasmic and Nuclear, Polymorphism, Single Nucleotide, Cytochrome P-450 CYP3A
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