Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Autor Moreira, Ricardo P. P. Google Scholar
Jorge, Alexander A. L. Google Scholar
Gomes, Larissa G. Google Scholar
Kaupert, Laura C. Google Scholar
Massud Filho, João Autor UNIFESP Google Scholar
Mendonca, Berenice B. Google Scholar
Bachega, Tânia A. S. S. Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo INTRODUCTION: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed. OBJECTIVE: The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. METHODS: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels. RESULTS: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose. CONCLUSION: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.
Palavra-chave 21-hydroxylase deficiency
Glucocorticoid replacement therapy
Pharmacogenetics
Polymorphism
CYP3A7*1C allele
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 05/04726-0
FAPESP: 09/54238-2
FAPESP: 09/54394-4
CNPq: 305117/2009-2
CNPq: 301477/2009-4
CNPq: 301339/2008-9
Data de publicação 2011-01-01
Publicado em Clinics. Faculdade de Medicina / USP, v. 66, n. 8, p. 1361-1366, 2011.
ISSN 1807-5932 (Sherpa/Romeo, fator de impacto)
Publicador Faculdade de Medicina / USP
Extensão 1361-1366
Fonte http://dx.doi.org/10.1590/S1807-59322011000800009
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000294822800009
SciELO S1807-59322011000800009 (estatísticas na SciELO)
Endereço permanente http://repositorio.unifesp.br/handle/11600/6201

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