The authors declare that they have no competing financial interests.
The effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia
Article first published online: 8 OCT 2012
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Special Issue: Variant
Volume 84, Issue 5, pages 482–488, November 2013
How to Cite
The effect of fetal androgen metabolism-related gene variants on external genitalia virilization in congenital adrenal hyperplasia., , , , , , , , , .
- Issue published online: 17 OCT 2013
- Article first published online: 8 OCT 2012
- Accepted manuscript online: 14 SEP 2012 12:20PM EST
- Manuscript Revised: 10 SEP 2012
- Manuscript Accepted: 10 SEP 2012
- Manuscript Received: 2 JUL 2012
- FAPESP. Grant Number: 2008/57616-5
- FAPESP. Grant Number: 2008/55546-0
- CNPq. Grant Numbers: 305117/2009-2, # 305743/2011-2
- 21-hydroxylase deficiency;
- CYP3A7, PXR and CAR allelic variants;
- external genitalia virilization;
- fetal androgen metabolism;
- genotype/phenotype correlation
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 (r2 = 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.