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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Faculdade de Medicina / USP 2011-01-01
• Series: Clinics
• Subjects: 21-hydroxylase deficiency; Glucocorticoid replacement therapy; Pharmacogenetics; Polymorphism; CYP3A7*1C allele
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322011000800009

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.