The effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia

The effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia

Author Kaupert, L. C. Google Scholar
Lemos-Marini, S. H. V. Google Scholar
Mello, Maricilda Palandi de Autor UNIFESP Google Scholar
Moreira, R. P. Google Scholar
Brito, V. N. Google Scholar
Jorge, A. A. L. Google Scholar
Longui, C. A. Google Scholar
Guerra, G. Google Scholar
Mendonca, B. B. Google Scholar
Bachega, T. A. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Abstract 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 CARSNVs on the genital phenotype in 21OHD females. Prader scores were evaluated in 183 patients. the CYP3A7, PXR and CARSNVs 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.
Keywords 21-hydroxylase deficiency
PXR and CAR allelic variants
external genitalia virilization
fetal androgen metabolism
phenotype correlation
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2008/57616-5
FAPESP: 2008/55546-0
CNPq: 305117/2009-2
CNPq: 305743/2011-2
Date 2013-11-01
Published in Clinical Genetics. Hoboken: Wiley-Blackwell, v. 84, n. 5, p. 482-488, 2013.
ISSN 0009-9163 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 482-488
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000328331600009

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