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

Autor(es)

Kaupert, L. C. ^[1] ; Lemos-Marini, S. H. V. ^[2] ; De Mello, M. P. ^[3] ; Moreira, R. P. ^[1] ; Brito, V. N. ^[1] ; Jorge, A. A. L. ^[1] ; Longui, C. A. ^[4] ; Guerra, Jr., G. ^[2] ; Mendonca, B. B. ^[1] ; Bachega, T. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM 42, Hosp Clin, Unidade Endocrinol Desenvolvimento, Disciplina End, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Unidade Endocrinol Pediat, Dept Pediat, Fac Ciencias Med, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Ctr Biol Mol & Engn Genet, Campinas, SP - Brazil

^[4] Irmandade Santa Casa de Misericordia Sao Paulo, Unidade Endocrinol Pediat, Dept Pediat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Genetics; v. 84, n. 5, p. 482-488, NOV 2013.
• Citações Web of Science: 6

Resumo

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. (AU)

• Processo FAPESP: 08/57616-5 - Análise de genes moduladores do fenótipo da forma clássica da deficiência da 21-hidroxilase
• Beneficiário: Tania Aparecida Sartori Sanchez Bachega
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/55546-0 - Análise de genes moduladores do fenótipo da forma clássica da deficiência da 21-hidroxilase
• Beneficiário: Laura Cesar Kaupert
• Linha de fomento: Bolsas no Brasil - Doutorado Direto