Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
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...
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doaj-3ce8e63f566f438699215588f1c131212020-11-24T22:01:20ZengFaculdade de Medicina / USPClinics1807-59321980-53222011-01-016681361136610.1590/S1807-59322011000800009Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiencyRicardo P. P. MoreiraAlexander A. L. JorgeLarissa G. GomesLaura C. KaupertJoão Massud FilhoBerenice B. MendoncaTânia A. S. S. BachegaINTRODUCTION: 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-5932201100080000921-hydroxylase deficiencyGlucocorticoid replacement therapyPharmacogeneticsPolymorphismCYP3A7*1C allele |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ricardo P. P. Moreira Alexander A. L. Jorge Larissa G. Gomes Laura C. Kaupert João Massud Filho Berenice B. Mendonca Tânia A. S. S. Bachega |
spellingShingle |
Ricardo P. P. Moreira Alexander A. L. Jorge Larissa G. Gomes Laura C. Kaupert João Massud Filho Berenice B. Mendonca Tânia A. S. S. Bachega Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency Clinics 21-hydroxylase deficiency Glucocorticoid replacement therapy Pharmacogenetics Polymorphism CYP3A7*1C allele |
author_facet |
Ricardo P. P. Moreira Alexander A. L. Jorge Larissa G. Gomes Laura C. Kaupert João Massud Filho Berenice B. Mendonca Tânia A. S. S. Bachega |
author_sort |
Ricardo P. P. Moreira |
title |
Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency |
title_short |
Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency |
title_full |
Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency |
title_fullStr |
Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency |
title_full_unstemmed |
Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency |
title_sort |
pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency |
publisher |
Faculdade de Medicina / USP |
series |
Clinics |
issn |
1807-5932 1980-5322 |
publishDate |
2011-01-01 |
description |
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. |
topic |
21-hydroxylase deficiency Glucocorticoid replacement therapy Pharmacogenetics Polymorphism CYP3A7*1C allele |
url |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322011000800009 |
work_keys_str_mv |
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