A Single Nucleotide Variant in the Promoter Region of 17 beta-HSD Type 5 Gene Influences External Genitalia Virilization in Females with 21-Hydroxylase Deficiency

Autor(es):Mostrar menos -

Kaupert, Laura C. ^[1] ; Gomes, Larissa G. ^[1] ; Brito, Vinicius N. ^[1] ; Lemos-Marini, Sofia H. V. ^[2] ; de Mello, Maricilda P. ^[3] ; Longui, Carlos A. ; Kochi, Cristiane ^[4] ; de Castro, Margaret ^[5] ; Guerra, Jr., Gil ^[2] ; Mendonca, Berenice B. ^[1] ; Bachega, Tania A. S. S. ^[1]

Afiliação do(s) autor(es)

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

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

^[3] Univ Estadual Campinas, Ctr Biol Mol & Engen Genet, Sao Paulo - Brazil

^[4] Santa Casa Sao Paulo, Dept Ciencias Fisiol, Fac Ciencias Med, Lab Med, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Dept Clin Med, BR-14049 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Hormone Research in Paediatrics; v. 85, n. 5, p. 333-338, 2016.
• Citações Web of Science: 3

Resumo

Background: In 21-hydroxylase deficiency (21-OHD), there is an influence of genotype on the severity of external genitalia virilization. However, females carrying mutations predicting a similar impairment of enzymatic activity present a wide variability of genital phenotypes. In such cases, interindividual variability in genes related to the sex steroid hormone pathway could play a role. Objective: To evaluate the influence of POR, HSD17B5 and SRD5A2 variants on the severity of external genitalia virilization in 21-OHD females. Design and Patients: Prader stages were evaluated in 178 females with 21-OHD from a multicenter study. The 21-OHD genotypes were divided into two groups according to their severity: severe and moderate. The influences of the POR p.A503V, HSD17B5 c.-71A>G, HSD17B5 c.-210A>C, and SRD5A2 p.A49T and p.V89L variants on the degree of external genitalia virilization were analyzed. Results: The POR p.A503V, HSD17B5 c.-71A>G, HSD17B5 c.-210A>C, and SRD5A2 p.A49T and p.V89L variants were found in 25, 33, 17, 1, and 31% of the alleles, respectively. In uni-and multilinear regression, HSD17B5 c.-210A>C has a significant influence on the degree of external genitalia virilization. This variant was also identified with a higher frequency in the most severely virilized females. Conclusion: We demonstrated that a variant in the promoter region of HSD17B5 related to fetal androgen synthesis influences the genital phenotype in 21-OHD females. (C) 2016 S. Karger AG, Basel (AU)

• Processo FAPESP: 14/07878-4 - Avaliação da eficácia dos diferentes testes diagnósticos no programa nacional de triagem neonatal (PNTN) da hiperplasia adrenal congênita por deficiência da 21-hidroxilase (HAC)
• Beneficiário: Tania Aparecida Sartori Sanchez Bachega
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular