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

Author(s)

Moreira, Ricardo P. P. ^[1] ; Jorge, Alexander A. L. ^[2] ; Gomes, Larissa G. ^[1] ; Kaupert, Laura C. ^[1] ; Massud Filho, Joao ^[3] ; Mendonca, Berenice B. ^[1] ; Bachega, Tania A. S. S. ^[1]

Affiliation

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

^[2] Univ Sao Paulo, Fac Med, Disciplina Endocrinol, Unidade Endocrinol Genet LIM 25, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Curso Especializacao Med Farmaceut, Sao Paulo - Brazil

• Document type: Journal article
• Source: Clinics; v. 66, n. 8, p. 1361-1365, 2011.
• Web of Science Citations: 5

Abstract

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 in glucocorticoid 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/m(2)/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. (AU)

• FAPESP's process: 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development
• Grantee: Ana Claudia Latronico Xavier
• Support Opportunities: Research Projects - Thematic Grants